1  2742 131 EXPOSURE TO THE PLASTICIZER, DI-(2-ETHYLHEXYL) PHTHALATE DURING JUVENILE PERIOD EXACERBATES AUTISM-LIKE BEHAVIOR IN ADULT BTBR T + TF/J MICE DUE TO DNA HYPOMETHYLATION AND ENHANCED INFLAMMATION IN BRAIN AND SYSTEMIC IMMUNE CELLS. EPIGENETIC MODIFICATIONS ARE KNOWN TO PLAY A CRUCIAL ROLE IN THE BEHAVIORAL MODIFICATIONS THROUGH REGULATION OF GENE EXPRESSION. ENVIRONMENTAL FACTORS ARE KNOWN TO REGULATE GENETIC TRANSCRIPTION THROUGH DNA METHYLATION WHICH IS ONE OF THE MECHANISMS OF EPIGENETIC MODIFICATION. DI-2-ETHYLHEXYL PHTHALATE (DEHP) IS ONE OF THE MOST ABUNDANT PHTHALATE PLASTICIZERS IN DAY-TO-DAY PRODUCTS. PRENATAL/POSTNATAL DEHP ADMINISTRATION HAS BEEN REPORTED TO CAUSE INFLAMMATION AS WELL AS BEHAVIORAL DYSREGULATION, HOWEVER IT IS NOT KNOWN IF EXPOSURE TO DEHP DURING JUVENILE STAGE AFFECTS PERIPHERAL/NEURONAL INFLAMMATION AND AUTISM-LIKE SYMPTOMS IN BTBR MICE AT ADULTHOOD. THIS STUDY INVESTIGATED EFFECT OF DEHP EXPOSURE DURING JUVENILE PERIOD ON DNA METHYLATION (GLOBAL DNA METHYLATION/DNMT1 EXPRESSION) AND INFLAMMATION (IL-17A, IL-6, MCP-1, TNF-ALPHA) IN CD4 + T CELLS/CD11C + DCS AND CORTEX, AND AUTISM-LIKE SYMPTOMS (THREE-CHAMBERED SOCIABILITY TEST, SELF-GROOMING AND MARBLE BURYING TEST) IN ASOCIAL BTBR AND SOCIAL C57 MICE AT ADULTHOOD. OUR DATA REVEAL THAT BTBR MICE EXPOSED TO DEHP DURING JUVENILE PERIOD HAVE HYPOMETHYLATED DNA/DNMT1 EXPRESSION IN CD11C + DCS AND CORTEX AS COMPARED TO VEHICLE-EXPOSED BTBR MICE. IT WAS ASSOCIATED WITH UPREGULATED INFLAMMATION IN PERIPHERY [PLASMA IL-6/IL-17A, CD11C + DCS (IL-6/MCP-1/TNF-ALPHA), AND CD4+ T CELLS (IL-17A)] AND CORTEX (IL-6, MCP-1, TNF-ALPHA), AND AGGRAVATION IN AUTISM-LIKE SYMPTOMS IN DEHP-TREATED BTBR MICE. THESE DATA PROPOSE THAT EXPOSURE OF DEHP DURING JUVENILE PERIOD MAY AFFECT AUTISM-LIKE BEHAVIOR AND INFLAMMATION IN BTBR MICE AT ADULTHOOD THROUGH EPIGENETIC REGULATION. THEREFORE, UNDERLYING GENETIC PREDISPOSITION MAY PLAY A CRUCIAL ROLE IN WORSENING OF AUTISTIC SYMPTOMS IN ASD SUBJECTS IN ADULTHOOD IF THEY ARE EXPOSED TO ENVIRONMENTAL POLLUTANTS SUCH AS DEHP DURING JUVENILE PERIOD.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
2   998  27 CHRONIC SUBCONVULSIVE ACTIVITY DURING EARLY POSTNATAL LIFE PRODUCES AUTISTIC BEHAVIOR IN THE ABSENCE OF NEUROTOXICITY IN THE JUVENILE WEANLING PERIOD. THE DIAGNOSIS OF AUTISM SPECTRUM DISORDER (ASD) VARIES FROM VERY MILD TO SEVERE SOCIAL AND COGNITIVE IMPAIRMENTS. WE HYPOTHESIZED THAT EPIGENETIC SUBCONVULSIVE ACTIVITY IN EARLY POSTNATAL LIFE MAY CONTRIBUTE TO THE DEVELOPMENT OF AUTISTIC BEHAVIOR IN A SEX-RELATED MANNER. LOW DOSES OF KAINIC ACID (KA) (25-100 MUG) WERE ADMINISTERED TO RAT PUPS FOR 15 DAYS BEGINNING ON POSTNATAL (P) DAY 6 TO CHRONICALLY ELEVATE NEURONAL ACTIVITY. A BATTERY OF CLASSICAL AND NOVEL BEHAVIORAL TESTS WAS USED, AND SEX DIFFERENCES WERE OBSERVED. OUR NOVEL OPEN HANDLING TEST REVEALED THAT ASD MALES NOSE POKED MORE OFTEN AND ASD FEMALES CLIMBED AND ESCAPED MORE FREQUENTLY WITH AGE. IN THE SOCIAL INTERACTION TEST, ASD MALES WERE LESS SOCIAL THAN ASD FEMALES WHO WERE MORE ANXIOUS IN HANDLING AND ELEVATED PLUS MAZE (EPM) TASKS. TO EVALUATE GROUP DYNAMICS, SIBLING AND NON-SIBLING CONTROL AND EXPERIMENTAL ANIMALS EXPLORED 3 DIFFERENT SHAPED NOVEL SOCIAL ENVIRONMENTS. CONTROL PUPS HUDDLED QUICKLY AND MORE FREQUENTLY IN ALL ENVIRONMENTS WHETHER THEY SOCIALIZED WITH LITTERMATES OR NON-SIBLINGS COMPARED TO ASD GROUPS. NON-SIBLING ASD PUPS WERE ERRATIC AND HUDDLED IN SMALLER GROUPS. IN THE OBJECT RECOGNITION TEST, ONLY ASD MALES SPENT LESS TIME WITH THE NOVEL OBJECT COMPARED TO CONTROL PUPS. DATA SUGGEST THAT CHRONIC SUBCONVULSIVE ACTIVITY IN EARLY POSTNATAL LIFE LEADS TO AN ASD PHENOTYPE IN THE ABSENCE OF CELL DEATH. MALES WERE MORE SUSCEPTIBLE TO DEVELOPING ASOCIAL BEHAVIORS AND COGNITIVE PATHOLOGIES, WHEREAS FEMALES WERE PRONE TO HIGHER LEVELS OF HYPERACTIVITY AND ANXIETY, VALIDATING OUR POSTNATAL ASD MODEL APPARENT IN THE PRE-JUVENILE PERIOD.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
3   168  23 ABNORMAL TRANSMETHYLATION/TRANSSULFURATION METABOLISM AND DNA HYPOMETHYLATION AMONG PARENTS OF CHILDREN WITH AUTISM. AN INTEGRATED METABOLIC PROFILE REFLECTS THE COMBINED INFLUENCE OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS THAT AFFECT THE CANDIDATE PATHWAY OF INTEREST. RECENT EVIDENCE SUGGESTS THAT SOME AUTISTIC CHILDREN MAY HAVE REDUCED DETOXIFICATION CAPACITY AND MAY BE UNDER CHRONIC OXIDATIVE STRESS. BASED ON REPORTS OF ABNORMAL METHIONINE AND GLUTATHIONE METABOLISM IN AUTISTIC CHILDREN, IT WAS OF INTEREST TO EXAMINE THE SAME METABOLIC PROFILE IN THE PARENTS. THE RESULTS INDICATED THAT PARENTS SHARE SIMILAR METABOLIC DEFICITS IN METHYLATION CAPACITY AND GLUTATHIONE-DEPENDENT ANTIOXIDANT/DETOXIFICATION CAPACITY OBSERVED IN MANY AUTISTIC CHILDREN. STUDIES ARE UNDERWAY TO DETERMINE WHETHER THE ABNORMAL PROFILE IN PARENTS REFLECTS LINKED GENETIC POLYMORPHISMS IN THESE PATHWAYS OR WHETHER IT SIMPLY REFLECTS THE CHRONIC STRESS OF COPING WITH AN AUTISTIC CHILD.	2008	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
4   267  27 AFFECTIVE AND COGNITIVE BEHAVIOR IN THE ALPHA-GALACTOSIDASE A DEFICIENT MOUSE MODEL OF FABRY DISEASE. FABRY DISEASE IS AN X-LINKED INHERITED LYSOSOMAL STORAGE DISORDER WITH INTRACELLULAR ACCUMULATION OF GLOBOTRIAOSYLCERAMIDE (GB3) DUE TO ALPHA-GALACTOSIDASE A (ALPHA-GAL A) DEFICIENCY. FABRY PATIENTS FREQUENTLY REPORT OF ANXIETY, DEPRESSION, AND IMPAIRED COGNITIVE FUNCTION. WE CHARACTERIZED AFFECTIVE AND COGNITIVE PHENOTYPE OF MALE MICE WITH ALPHA-GAL A DEFICIENCY (FABRY KO) AND COMPARED RESULTS WITH THOSE OF AGE-MATCHED MALE WILDTYPE (WT) LITTERMATES. YOUNG (3 MONTHS) AND OLD (>/= 18 MONTHS) MICE WERE TESTED IN THE NAIVE STATE AND AFTER I.PL. INJECTION OF COMPLETE FREUND;S ADJUVANT (CFA) AS AN INFLAMMATORY PAIN MODEL. WE USED THE ELEVATED PLUS MAZE (EPM), THE LIGHT-DARK BOX (LDB) AND THE OPEN FIELD TEST (OF) TO INVESTIGATE ANXIETY-LIKE BEHAVIOR. THE FORCED SWIM TEST (FST) AND MORRIS WATER MAZE (MWM) WERE APPLIED TO ASSESS DEPRESSIVE-LIKE AND LEARNING BEHAVIOR. THE EPM TEST REVEALED NO INTERGROUP DIFFERENCE FOR ANXIETY-LIKE BEHAVIOR IN NAIVE YOUNG AND OLD FABRY KO MICE COMPARED TO WT LITTERMATES, EXCEPT FOR LONGER TIME SPENT IN OPEN ARMS OF THE EPM FOR YOUNG WT MICE COMPARED TO YOUNG FABRY KO MICE (P<0.05). AFTER CFA INJECTION, YOUNG FABRY KO MICE SHOWED INCREASED ANXIETY-LIKE BEHAVIOR COMPARED TO YOUNG WT LITTERMATES (P<0.05) AND NAIVE YOUNG FABRY KO MICE (P<0.05) IN THE EPM AS REFLECTED BY SHORTER TIME SPENT IN EPM OPEN ARMS. THERE WERE NO RELEVANT DIFFERENCES IN THE LDB AND THE OF TEST, EXCEPT FOR LONGER TIME SPENT IN THE CENTER ZONE OF THE OF BY YOUNG WT MICE COMPARED TO YOUNG FABRY KO MICE (P<0.05). COMPLEMENTARY TO THIS, DEPRESSION-LIKE AND LEARNING BEHAVIOR WERE NOT DIFFERENT BETWEEN GENOTYPES AND AGE-GROUPS, EXCEPT FOR THE EXPECTEDLY LOWER MEMORY PERFORMANCE IN OLDER AGE-GROUPS COMPARED TO YOUNG MICE. OUR RESULTS INDICATE THAT GENETIC INFLUENCES ON AFFECTIVE AND COGNITIVE SYMPTOMS IN FD MAY BE OF SUBORDINATE RELEVANCE, DRAWING ATTENTION TO POTENTIAL INFLUENCES OF ENVIRONMENTAL AND EPIGENETIC FACTORS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
5  4857  32 OPTOGENETIC STIMULATION OF THE ANTERIOR CINGULATE CORTEX AMELIORATES AUTISTIC-LIKE BEHAVIORS IN RATS INDUCED BY NEONATAL ISOLATION, CAUDATE PUTAMEN AS A SITE FOR ALTERATION. EPIGENETIC AGENTS, SUCH AS NEONATAL ISOLATION DURING NEURODEVELOPMENTAL PERIOD OF LIFE, CAN CHANGE VARIOUS REGIONS OF THE BRAIN. IT MAY FURTHER INDUCE PSYCHOLOGICAL DISORDERS SUCH AS AUTISTIC-LIKE PHENOMENA. THIS STUDY INDICATED THE ROLE OF CHRONIC INCREASED ANTERIOR CINGULATE CORTEX (ACC) OUTPUT ON ALTERATION OF CAUDATE PUTAMEN (CPU) AS A MAIN BEHAVIOR REGULATOR REGION OF THE BRAIN IN ADULT MATERNAL DEPRIVED (MD) RATS. FOR MAKING AN ANIMAL MODEL, NEONATES WERE ISOLATED FROM THEIR MOTHERS IN POSTNATAL DAYS (PND 1-10, 3 H/DAY). SUBSEQUENTLY, THEY BILATERALLY RECEIVED PLENTI-CAMKIIA-HCHR2 (H134R)-MCHERRY-WPRE VIRUS IN ACC AREA VIA STEREOTAXIC SURGERY IN PND50. AFTER 22 DAYS, THESE REGIONS WERE EXPOSED TO BLUE LASER (473 NM) FOR SIX CONSECUTIVE DAYS (15 MIN/DAY). THEN, BEHAVIORAL DEFICITS WERE TESTED AND WERE COMPARED WITH CONTROL GROUP IN THE FOLLOWING DAY. ANIMALS WERE IMMEDIATELY KILLED AND THEIR BRAINS WERE PREPARED FOR TISSUE PROCESSING. RESULTS SHOWED THAT NEONATAL ISOLATION INDUCES AUTISTIC-LIKE BEHAVIORS AND LEADS TO OVEREXPRESSION OF NMDAR1 AND NOX2-GP91(PHOX) PROTEINS AND ELEVATION OF CATALASE ACTIVITY IN THE CPU REGIONS OF THE ADULT OFFSPRING COMPARED WITH CONTROL GROUP. CHRONIC OPTOGENETIC STIMULATION OF ACC NEURONS CONTAINING (CHR2+) LED TO SIGNIFICANT REDUCTION IN THE APPEARANCE OF STEREOTYPICAL BEHAVIOR AND ALIEN-PHOBIA IN MD RATS. THE AMOUNT OF NMDAR1 AND NOX2-GP91(PHOX) EXPRESSION AND THE CATALASE ACTIVITY IN CPU WERE REDUCED AFTER THIS TREATMENT. THEREFORE, AUTISTIC-LIKE BEHAVIOR SEEMS TO BE RELATED WITH ELEVATION OF NMDAR1 AND NOX2-GP91(PHOX) PROTEIN LEVELS THAT ENHANCE THE EFFECT OF GLUTAMATERGIC PROJECTION ON CPU REGIONS. OPTOGENETIC TREATMENT ALSO COULD AMELIORATE BEHAVIORAL DEFICITS BY MODULATING THESE PROTEIN DENSITIES.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
6  4939  30 PATERNAL NICOTINE EXPOSURE IN RATS PRODUCES LONG-LASTING NEUROBEHAVIORAL EFFECTS IN THE OFFSPRING. STUDIES OF INTERGENERATIONAL EFFECTS OF PARENTAL CHEMICAL EXPOSURE HAVE PRINCIPALLY FOCUSED ON MATERNAL EXPOSURE, PARTICULARLY FOR STUDIES OF ADVERSE NEUROBEHAVIORAL CONSEQUENCES ON THE OFFSPRING. MATERNAL NICOTINE EXPOSURE HAS LONG BEEN KNOWN TO CAUSE ADVERSE NEUROBEHAVIORAL EFFECTS ON THE OFFSPRING. HOWEVER, PATERNAL TOXICANT EXPOSURE HAS ALSO BEEN FOUND TO CAUSE NEUROBEHAVIORAL TOXICITY IN THEIR OFFSPRING. RECENT WORK SUGGESTS THAT PATERNAL NICOTINE EXPOSURE CAN HAVE EPIGENETIC EFFECTS, ALTHOUGH IT REMAINS UNCLEAR WHETHER SUCH CHANGES LEAD TO NEUROBEHAVIORAL EFFECTS. IN THE CURRENT STUDY, WE INVESTIGATED THE EFFECTS OF PATERNAL NICOTINE EXPOSURE ON NEUROBEHAVIORAL DEVELOPMENT OF THEIR OFFSPRING. MALE SPRAGUE-DAWLEY RATS WERE EXPOSED TO 0 OR 2 MG/KG/DAY NICOTINE (SC) FOR 56 CONSECUTIVE DAYS WITH TWO CONSECUTIVE 2ML4 OSMOTIC MINIPUMPS. FOLLOWING TREATMENT, THESE MALES WERE MATED WITH DRUG-NAIVE FEMALE RATS. OFFSPRING OF BOTH SEXES WERE TESTED IN A BEHAVIORAL BATTERY TO ASSESS LOCOMOTION, EMOTIONAL FUNCTION AND COGNITION. PATERNAL NICOTINE EXPOSURE DID NOT IMPACT OFFSPRING VIABILITY, HEALTH OR GROWTH. HOWEVER, BEHAVIORAL FUNCTION OF THE OFFSPRING WAS SIGNIFICANTLY ALTERED BY PATERNAL NICOTINE EXPOSURE. MALE OFFSPRING WITH PATERNAL NICOTINE EXPOSURE EXHIBITED LOCOMOTOR HYPERACTIVITY IN THE FIGURE-8 APPARATUS WHEN TESTED DURING ADOLESCENCE. WHEN RETESTED IN ADULTHOOD AND REGARDLESS OF SEX, OFFSPRING OF THE NICOTINE EXPOSED FATHER SHOWED SIGNIFICANTLY REDUCED HABITUATION OF LOCOMOTOR ACTIVITY OVER THE COURSE OF THE SESSION. COMPARED TO CONTROLS, FEMALE OFFSPRING OF NICOTINE-EXPOSED FATHERS SHOWED SIGNIFICANTLY REDUCED RESPONSE LATENCY IN THE RADIAL ARM MAZE TEST. IN ADDITION TO LOCOMOTOR HYPERACTIVITY, THE OFFSPRING OF NICOTINE-EXPOSED FATHERS ALSO SHOWED SIGNIFICANTLY DIMINISHED HABITUATION IN THE NOVEL OBJECT RECOGNITION TEST. THESE RESULTS INDICATE THAT CHRONIC PATERNAL NICOTINE EXPOSURE CAN IMPACT THE BEHAVIOR OF OFFSPRING, PRODUCING LOCOMOTOR HYPERACTIVITY AND IMPAIRED HABITUATION.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
7  1740  29 EARLY ENRICHED ENVIRONMENT PREVENTS EPIGENETIC P11 GENE CHANGES INDUCED BY ADULTHOOD STRESS IN MICE. POSITIVE EXPERIENCES IN EARLY LIFE MAY IMPROVE THE CAPACITY TO COPE WITH ADULTHOOD STRESS THROUGH EPIGENETIC MODIFICATION. WE INVESTIGATED WHETHER AN ENRICHED ENVIRONMENT (EE) IN THE POSTNATAL PERIOD AFFECTED EPIGENETIC CHANGES IN THE P11 GENE INDUCED BY CHRONIC UNPREDICTABLE STRESS (CUS) IN ADULT C57BL/6J MICE. EE WAS INTRODUCED FOR 5 WEEKS DURING POSTNATAL DAYS 21-55. AFTER EE, THE MICE WERE SUBJECTED TO CUS FOR 4 WEEKS. EE PREVENTED DEPRESSION-LIKE BEHAVIOR INDUCED BY ADULT CUS. EE PREVENTED A DECREASE IN P11 MRNA AND HISTONE H3 ACETYLATION INDUCED BY CUS, WITH CHANGES IN THE EXPRESSION OF HISTONE DEACETYLASE 5. MOREOVER, EE PREVENTED CHANGES IN TRIMETHYLATION OF HISTONE H3 LYSINE 4 (H3K4) AND H3K27 INDUCED BY CUS. FURTHERMORE, EE HAD POSITIVE EFFECTS ON BEHAVIOR AND EPIGENETIC ALTERATIONS IN ADULT MICE WITHOUT CUS. THESE RESULTS SUGGEST THAT ONE OF THE UNDERLYING MECHANISMS OF EARLY-LIFE EE MAY INVOLVE EPIGENETIC MODIFICATION OF THE HIPPOCAMPAL P11 GENE PROMOTER.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
8  1548  39 DNA METHYLATION IN THE DEVELOPING HIPPOCAMPUS AND AMYGDALA OF ANXIETY-PRONE VERSUS RISK-TAKING RATS. ALL ORGANISMS EXHIBIT A WIDE RANGE OF EMOTIONAL BEHAVIORS AND INTERACT WITH THE ENVIRONMENT IN DIFFERENT WAYS. SOME INDIVIDUALS MAY BE MORE QUIET AND SHY WHEREAS OTHERS ARE MORE OUTGOING AND ADVENTUROUS. THESE TEMPERAMENTAL AND PERSONALITY DIFFERENCES CAN PREDISPOSE INDIVIDUALS TO CERTAIN PSYCHOPATHOLOGIES WHICH MAY BE INFLUENCED BY GENETIC VULNERABILITY AND/OR EARLY LIFE EXPERIENCES. RODENT MODELS CAN BE USED TO RECAPITULATE EMOTIONAL REACTIVITY DIFFERENCES, AND THESE MODELS CAN, IN TURN, BE USED TO EXAMINE POTENTIAL NEUROBIOLOGICAL UNDERPINNINGS OF THESE TRAITS. THE PRESENT STUDY UTILIZES TWO STRAINS OF RATS THAT WERE SELECTIVELY BRED FOR DIFFERENCES IN NOVELTY SEEKING. HIGH NOVELTY-RESPONDING (BHR) RATS ARE VERY ACTIVE IN RESPONSE TO NOVELTY, EXHIBIT EXAGGERATED RISK-TAKING, AGGRESSION, IMPULSIVITY, AND SHOW INCREASED BEHAVIORAL RESPONSE TO COCAINE. LOW NOVELTY-RESPONDING (BLR) RATS SHOW INCREASED ANXIETY, DEPRESSIVE BEHAVIOR AND VULNERABILITY TO CHRONIC STRESS. ONE WAY IN WHICH THE BHR VERSUS BLR BEHAVIORAL PHENOTYPES MAY DIFFER IS THROUGH EPIGENETIC MODIFICATION OF DNA. DNA CAN BE MODIFIED THROUGH PROCESSES SUCH AS ACETYLATION OR METHYLATION TO EITHER ENHANCE OR SUBDUE GENE EXPRESSION. THIS STUDY EXAMINES PUTATIVE DIFFERENCES IN METHYLATION LEVELS IN THE HIPPOCAMPUS AND AMYGDALA OF DEVELOPING BHR-BLR RATS. PREVIOUS RESEARCH OBSERVED WIDESPREAD GENE EXPRESSION DIFFERENCES IN THE BLR DEVELOPING HIPPOCAMPUS, AND THE CURRENT STUDY AIMS TO BEGIN TO EXAMINE POTENTIAL EPIGENETIC FACTORS THAT MAY CONTRIBUTE TO THOSE GENE DIFFERENCES. THE AMYGDALA WAS CHOSEN BECAUSE IT IS INVOLVED IN EMOTIONAL PROCESSES, IN PART THROUGH ITS CONNECTIONS WITH THE HIPPOCAMPUS. THEREFORE, THE PRESENT STUDY USED IN SITU HYBRIDIZATION TO ASSESS THE EXPRESSION OF DNA METHYLTRANSFERASE-1 (DNMT1) MRNA IN THE HIPPOCAMPUS, AMYGDALA AND SEVERAL OTHER BRAIN AREAS OF BHR AND BLR PUPS AT THREE DEVELOPMENTAL TIME POINTS: POSTNATAL DAYS (P) 7, 14, AND 21. WE FOCUSED ON THE FIRST 3 POSTNATAL WEEKS, IN PART TO PARALLEL OUR EARLY MICROARRAY GENE EXPRESSION WORK, AND BECAUSE THIS REPRESENTS A CRITICAL PERIOD OF BRAIN DEVELOPMENT, WHICH SHAPES INDIVIDUALS' LIFELONG EMOTIONAL AND STRESS REACTIVITY. WE FOUND SIGNIFICANT DIFFERENCES IN DENTATE GYRUS AND CA3 REGIONS OF THE HIPPOCAMPUS AT P7 WITH NO DIFFERENCES SEEN AT P14 OR P21. INTERESTINGLY, WE ALSO FOUND SIGNIFICANT BHR-BLR DNMT1 DIFFERENCES AT P7 WITHIN THE LATERAL, BASOLATERAL AND MEDIAL NUCLEI OF THE AMYGDALA, WITH NO DIFFERENCE AT P14 AND P21, SUGGESTING THAT THE FIRST POSTNATAL WEEK IS A CRITICAL PERIOD FOR DNA METHYLATION DURING BRAIN DEVELOPMENT.	2012	

9  3977  36 LONG-TERM EFFECT OF POST-TRAUMATIC STRESS IN ADOLESCENCE ON DENDRITE DEVELOPMENT AND H3K9ME2/BDNF EXPRESSION IN MALE RAT HIPPOCAMPUS AND PREFRONTAL CORTEX. EXPOSURE TO A HARSH ENVIRONMENT IN EARLY LIFE INCREASES IN THE RISK OF POST-TRAUMATIC STRESS DISORDER (PTSD) OF AN INDIVIDUAL. BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) PLAYS AN IMPORTANT ROLE IN NEURODEVELOPMENT IN DEVELOPMENTAL STAGES. BOTH CHRONIC AND TRAUMATIC STRESSES INDUCE A DECREASE IN THE LEVEL OF BDNF AND REDUCE NEURAL PLASTICITY, WHICH IS LINKED TO THE PATHOGENESIS OF PTSD. ALSO, STUDIES HAVE SHOWN THAT STRESS ALTERS THE EPIGENETIC MARKER H3K9ME2, WHICH CAN BIND TO THE PROMOTER REGION OF THE BDNF GENE AND REDUCE BDNF PROTEIN LEVEL. HOWEVER, THE LONG-TERM EFFECTS OF TRAUMATIC STRESS DURING ADOLESCENCE ON H3K9ME2, BDNF EXPRESSION AND DENDRITE DEVELOPMENT ARE NOT WELL-KNOWN. THE PRESENT STUDY ESTABLISHED A MODEL OF PTSD IN ADOLESCENT RATS USING AN INESCAPABLE FOOT SHOCK (IFS) PROCEDURE. ANXIETY-LIKE BEHAVIORS, SOCIAL INTERACTION BEHAVIOR AND MEMORY FUNCTION WERE ASSESSED BY THE OPEN FIELD TEST, ELEVATED PLUS MAZE TEST, THREE-CHAMBER SOCIABILITY TEST AND MORRIS WATER MAZE TEST. IN ADDITION, NEURONAL DEVELOPMENT AND H3K9ME2/BDNF EXPRESSION IN HIPPOCAMPUS (HIP) AND PREFRONTAL CORTEX (PFC) WERE EVALUATED BY GOLGI STAINING, WESTERN BLOTTING, QRT-PCR ANALYSIS AND CHIP-QPCR ANALYSIS. ADDITIONALLY, THE UNC0642, A SMALL MOLECULE INHIBITOR OF HISTONE METHYLTRANSFERASE (EHMT2) WAS USED FOR INTERVENTION. THE RESULTS SHOWED THAT THE IFS PROCEDURE INDUCED THE PTSD-LIKE BEHAVIORS IN RATS, RESULTED IN FEWER DENDRITE BRANCHES AND SHORTER DENDRITE LENGTH IN CA1 OF HIP AND PFC, INCREASED H3K9ME2 LEVEL AND DECREASED BDNF EXPRESSION IN HIP AND PFC. ALSO, ALTHOUGH ALL THE CHANGES CAN PERSIST TO ADULTHOOD, UNC0642 ADMINISTRATION RELIEVED MOST OF ALTERATIONS. OUR STUDY SUGGESTS THAT TRAUMATIC STRESS IN ADOLESCENCE LEADS TO IMMEDIATE AND LONG-TERM MENTAL DISORDERS, NEURONAL MORPHOLOGICAL CHANGES, LOWER BDNF LEVEL AND INCREASED H3K9ME2 LEVEL IN THE HIP AND PFC, INDICATING THAT H3K9ME2/BDNF DYSFUNCTION PLAYS A KEY ROLE IN PATHOGENESIS OF PTSD.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
10  4068  23 MATERNAL ANDROGEN EXCESS AND OBESITY INDUCE SEXUALLY DIMORPHIC ANXIETY-LIKE BEHAVIOR IN THE OFFSPRING. MATERNAL POLYCYSTIC OVARY SYNDROME (PCOS), A CONDITION ASSOCIATED WITH HYPERANDROGENISM, IS SUGGESTED TO INCREASE ANXIETY-LIKE BEHAVIOR IN THE OFFSPRING. BECAUSE PCOS IS CLOSELY LINKED TO OBESITY, WE INVESTIGATED THE IMPACT OF AN ADVERSE HORMONAL OR METABOLIC MATERNAL ENVIRONMENT AND OFFSPRING OBESITY ON ANXIETY IN THE OFFSPRING. THE OBESE PCOS PHENOTYPE WAS INDUCED BY CHRONIC HIGH-FAT-HIGH-SUCROSE (HFHS) CONSUMPTION TOGETHER WITH PRENATAL DIHYDROTESTOSTERONE EXPOSURE IN MOUSE DAMS. ANXIETY-LIKE BEHAVIOR WAS ASSESSED IN ADULT OFFSPRING WITH THE ELEVATED-PLUS MAZE AND OPEN-FIELD TESTS. THE INFLUENCE OF MATERNAL ANDROGENS AND MATERNAL AND OFFSPRING DIET ON GENES IMPLICATED IN ANXIETY WERE ANALYZED IN THE AMYGDALA AND HYPOTHALAMUS WITH REAL-TIME PCR ( N = 47). INDEPENDENT OF DIET, FEMALE OFFSPRING EXPOSED TO MATERNAL ANDROGENS WERE MORE ANXIOUS AND DISPLAYED UP-REGULATION OF ADRENOCEPTOR ALPHA 1B IN THE AMYGDALA AND UP-REGULATION OF HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE ( CRH). BY CONTRAST, MALE OFFSPRING EXPOSED TO A HFHS MATERNAL DIET HAD INCREASED ANXIETY-LIKE BEHAVIOR AND SHOWED UP-REGULATION OF EPIGENETIC MARKERS IN THE AMYGDALA AND UP-REGULATION OF HYPOTHALAMIC CRH. OVERALL, THERE WERE SUBSTANTIAL SEX DIFFERENCES IN GENE EXPRESSION IN THE BRAIN. THESE FINDINGS PROVIDE NOVEL INSIGHT INTO HOW MATERNAL ANDROGENS AND OBESITY EXERT SEX-SPECIFIC EFFECTS ON BEHAVIOR AND GENE EXPRESSION IN THE OFFSPRING OF A PCOS MOUSE MODEL.-MANTI, M., FORNES, R., QI, X., FOLMERZ, E., LINDEN HIRSCHBERG, A., DE CASTRO BARBOSA, T., MALIQUEO, M., BENRICK, A., STENER-VICTORIN, E. MATERNAL ANDROGEN EXCESS AND OBESITY INDUCE SEXUALLY DIMORPHIC ANXIETY-LIKE BEHAVIOR IN THE OFFSPRING.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
11  1761  29 EARLY STRESS EVOKES AGE-DEPENDENT BIPHASIC CHANGES IN HIPPOCAMPAL NEUROGENESIS, BDNF EXPRESSION, AND COGNITION. BACKGROUND: ADULT-ONSET STRESSORS EXERT OPPOSING EFFECTS ON HIPPOCAMPAL NEUROGENESIS AND COGNITION, WITH ENHANCEMENT OBSERVED FOLLOWING MILD STRESS AND DYSFUNCTION FOLLOWING SEVERE CHRONIC STRESS. WHILE EARLY LIFE STRESS EVOKES PERSISTENT CHANGES IN ANXIETY, IT IS UNKNOWN WHETHER EARLY STRESS DIFFERENTIALLY REGULATES HIPPOCAMPAL NEUROGENESIS, TROPHIC FACTOR EXPRESSION, AND COGNITION ACROSS THE LIFE SPAN. METHODS: HIPPOCAMPAL-DEPENDENT COGNITIVE BEHAVIOR, NEUROGENESIS, AND EPIGENETIC REGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) EXPRESSION WAS EXAMINED AT DISTINCT TIME POINTS ACROSS THE LIFE SPAN IN RATS SUBJECTED TO THE EARLY STRESS OF MATERNAL SEPARATION (ES) AND CONTROL GROUPS. WE ALSO EXAMINED THE INFLUENCE OF CHRONIC ANTIDEPRESSANT TREATMENT ON THE NEUROGENIC, NEUROTROPHIC, AND COGNITIVE CHANGES IN MIDDLE-AGED ES ANIMALS. RESULTS: ANIMALS SUBJECTED TO EARLY STRESS OF MATERNAL SEPARATION EXAMINED DURING POSTNATAL LIFE AND YOUNG ADULTHOOD EXHIBITED ENHANCED HIPPOCAMPAL NEUROGENESIS, DECREASED REPRESSIVE HISTONE METHYLATION AT THE BDNF IV PROMOTER ALONG WITH ENHANCED BDNF LEVELS, AND IMPROVED PERFORMANCE ON THE STRESS-ASSOCIATED MORRIS WATER MAZE. STRIKINGLY, OPPOSING CHANGES IN HIPPOCAMPAL NEUROGENESIS AND EPIGENETIC REGULATION OF BDNF IV EXPRESSION, CONCOMITANT WITH IMPAIRMENTS ON HIPPOCAMPAL-DEPENDENT COGNITIVE TASKS, WERE OBSERVED IN MIDDLE-AGED ES ANIMALS. CHRONIC ANTIDEPRESSANT TREATMENT WITH AMITRIPTYLINE ATTENUATED THE MALADAPTIVE NEUROGENIC, EPIGENETIC, TRANSCRIPTIONAL, AND COGNITIVE EFFECTS IN MIDDLE-AGED ES ANIMALS. CONCLUSIONS: OUR STUDY PROVIDES NOVEL INSIGHTS INTO THE SHORT- AND LONG-TERM CONSEQUENCES OF ES, DEMONSTRATING BOTH BIPHASIC AND UNIQUE, AGE-DEPENDENT CHANGES AT THE MOLECULAR, EPIGENETIC, NEUROGENIC, AND BEHAVIORAL LEVELS. THESE RESULTS INDICATE THAT EARLY STRESS MAY TRANSIENTLY ENDOW ANIMALS WITH A POTENTIAL ADAPTIVE ADVANTAGE IN STRESSFUL ENVIRONMENTS BUT ACROSS A LIFE SPAN IS ASSOCIATED WITH LONG-TERM DELETERIOUS EFFECTS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
12  3610  31 IN UTERO EXPOSURE TO ENDOCRINE-DISRUPTING CHEMICALS, MATERNAL FACTORS AND ALTERATIONS IN THE EPIGENETIC LANDSCAPE UNDERLYING LATER-LIFE HEALTH EFFECTS. WIDESPREAD PERSISTENCE OF ENDOCRINE-DISRUPTING CHEMICALS (EDCS) IN THE ENVIRONMENT HAS MANDATED THE NEED TO STUDY THEIR POTENTIAL EFFECTS ON AN INDIVIDUAL'S LONG-TERM HEALTH AFTER BOTH ACUTE AND CHRONIC EXPOSURE PERIODS. IN THIS REVIEW ARTICLE A PARTICULAR FOCUS IS GIVEN ON IN UTERO EXPOSURE TO EDCS IN RODENT MODELS WHICH RESULTED IN ALTERED EPIGENETIC PROGRAMMING AND TRANSGENERATIONAL EFFECTS IN THE OFFSPRING CAUSING DISRUPTED REPRODUCTIVE AND METABOLIC PHENOTYPES. THE LITERATURE TO DATE ESTABLISHES THE IMPACT OF TRANSGENERATIONAL EFFECTS OF EDCS POTENTIALLY ASSOCIATED WITH EPIGENETIC MEDIATED MECHANISMS. THEREFORE, THIS REVIEW AIMS TO PROVIDE A COMPREHENSIVE OVERVIEW OF EPIGENETIC PROGRAMMING AND IT'S REGULATION IN MAMMALS, PRIMARILY FOCUSING ON THE EPIGENETIC PLASTICITY AND SUSCEPTIBILITY TO EXOGENOUS HORMONE ACTIVE CHEMICALS DURING THE EARLY DEVELOPMENTAL PERIOD. FURTHER, WE HAVE ALSO IN DEPTH DISCUSSED THE EPIGENETIC ALTERATIONS ASSOCIATED WITH THE EXPOSURE TO SELECTED EDCS SUCH AS BISPHENOL A (BPA), DI-2-ETHYLHEXYL PHTHALATE (DEHP) AND VINCLOZLIN UPON IN UTERO EXPOSURE ESPECIALLY IN RODENT MODELS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
13  5020  35 PERSISTENT OVEREXPRESSION OF DNA METHYLTRANSFERASE 1 ATTENUATING GABAERGIC INHIBITION IN BASOLATERAL AMYGDALA ACCOUNTS FOR ANXIETY IN RAT OFFSPRING EXPOSED PERINATALLY TO LOW-DOSE BISPHENOL A. SUBSTANTIAL EVIDENCE INDICATES THAT PREDISPOSITION TO DISEASES CAN BE ACQUIRED DURING EARLY STAGES OF DEVELOPMENT AND INTERACTIONS BETWEEN ENVIRONMENTAL AND GENETIC FACTORS MAY BE IMPLICATED IN THE ONSET OF MANY PATHOLOGICAL CONDITIONS. WE HAVE SHOWN THAT PERINATAL EXPOSURE TO BISPHENOL A (BPA) AT ENVIRONMENTAL DOSE LEVEL CAUSES LONG-TERM ANXIETY-LIKE BEHAVIORS IN RATS. THE AIM OF THIS STUDY WAS TO EXAMINE EPIGENETIC REPROGRAMMING EFFECT OF BPA ON ANXIETY-RELATED NEUROBEHAVIOR IN THE RAT OFFSPRING. THE RESULTS OF REAL-TIME RT-PCR DISPLAYED THAT THE OVEREXPRESSION OF DNA METHYLTRANSFERASE 1 (DNMT1) MRNA WAS ACCOMPANIED BY THE REDUCTION OF GLUTAMIC ACID DECARBOXYLASE 67 (GAD67) MRNA LEVEL IN THE BASOLATERAL AMYGDALA (BLA) OF POSTNATAL DAY 45 BPA-EXPOSED FEMALE RATS. CHRONIC INTRO-BLA INJECTION WITH 5-ADA-CDR COULD RECTIFY THE GAD67 MRNA EXPRESSION. BEHAVIORAL DATA SHOWED THAT THE ANXIETY-LIKE BEHAVIORS IN BPA-EXPOSED RATS WERE REVERSED BY INTRO-BLA TREATMENT WITH 5-ADA-CDR WHICH COULD BE FURTHER BLOCKED BY PTX. ELECTROPHYSIOLOGICAL STUDY REVEALED BEHAVIORAL ALTERATIONS WERE ASSOCIATED WITH THE INCREASE OF POSTSYNAPTIC NEURONAL EXCITABILITY IN THE CORTICAL-BLA PATHWAY WHICH APPEARED AS MULTISPIKE RESPONSES, PAIRED-PULSE FACILITATION INSTEAD OF PAIRED-PULSE INHIBITION AND LONG-TERM POTENTIATION AND 5-AZA-CDR TREATMENT RESTORED THE INCREASED SYNAPTIC TRANSMISSION IN THE BLA VIA IMPROVING GABAERGIC SYSTEM. THE ABOVE RESULTS SUGGEST THAT THE OVEREXPRESSION OF DNMT1 IN THE BLA IS RESPONSIBLE FOR THE ETIOLOGY OF ANXIETY ASSOCIATED WITH BPA EXPOSURE VIA GABAERGIC DISINHIBITION. IN ADDITION, WE ALSO FIND THESE LONG-TERM NEUROBEHAVIORAL EFFECTS OF DEVELOPMENTAL BPA EXPOSURE ARE REVERSIBLE IN ADOLESCENT PERIOD.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
14  5752  28 SOCIAL ISOLATION AND SOCIAL SUPPORT AT ADULTHOOD AFFECT EPIGENETIC MECHANISMS, BRAIN-DERIVED NEUROTROPHIC FACTOR LEVELS AND BEHAVIOR OF CHRONICALLY STRESSED RATS. EPIGENETIC MODULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) PROVIDES ONE POSSIBLE EXPLANATION FOR THE DYSFUNCTIONS INDUCED BY STRESS, SUCH AS PSYCHIATRIC DISORDERS AND COGNITIVE DECLINE. INTERESTINGLY, SOCIAL SUPPORT CAN BE PROTECTIVE AGAINST SOME OF THESE EFFECTS, BUT THE MECHANISMS OF SOCIAL BUFFERING ARE POORLY UNDERSTOOD. CONVERSELY, EARLY ISOLATION EXACERBATES THE RESPONSES TO STRESSORS, ALTHOUGH ITS EFFECTS IN ADULTHOOD REMAIN UNCLEAR. THIS STUDY INVESTIGATED THE EFFECTS OF SOCIAL ISOLATION AND SOCIAL BUFFERING ON HIPPOCAMPAL EPIGENETIC MECHANISMS, BDNF LEVELS AND BEHAVIORAL RESPONSES OF CHRONICALLY STRESSED YOUNG ADULT RATS. MALE WISTAR RATS (3 MONTHS) WERE ASSIGNED TO ACCOMPANIED (PAIRED) OR ISOLATED HOUSING. AFTER ONE-MONTH HALF OF EACH GROUP WAS SUBMITTED TO A CHRONIC UNPREDICTABLE STRESS (CUS) PROTOCOL FOR 18 DAYS. AMONG ACCOMPANIED ANIMALS, ONLY ONE WAS EXPOSED TO STRESS. BEHAVIORAL ANALYSIS ENCOMPASSED THE OPEN FIELD, PLUS MAZE AND INHIBITORY AVOIDANCE TASKS. HIPPOCAMPAL H3K9 AND H4K12 ACETYLATION, HDAC5 EXPRESSION AND BDNF LEVELS WERE EVALUATED. ISOLATED HOUSING INCREASED HDAC5 EXPRESSION, DECREASED H3K9 AND H4K12 ACETYLATION, REDUCED BDNF LEVELS, AND IMPAIRED LONG-TERM MEMORY. STRESS AFFECTED WEIGHT GAIN, INDUCED ANXIETY-LIKE BEHAVIOR AND DECREASED ACK9H3 LEVELS. INTERACTIONS BETWEEN HOUSING CONDITIONS AND SOCIAL STRESS WERE SEEN ONLY FOR HDAC5 EXPRESSION, WHICH SHOWED A FURTHER INCREASE IN THE ISOLATED + CUS GROUP BUT REMAINED CONSTANT IN ACCOMPANIED ANIMALS. IN CONCLUSION, SOCIAL ISOLATION AT ADULTHOOD INDUCED EPIGENETIC ALTERATIONS AND EXACERBATED THE EFFECTS OF CHRONIC STRESS ON HDAC5. NOTWITHSTANDING, SOCIAL SUPPORT COUNTERACTED THE ADVERSE EFFECTS OF STRESS ON HDAC5 EXPRESSION.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
15  4935  25 PATERNAL COCAINE TAKING ELICITS EPIGENETIC REMODELING AND MEMORY DEFICITS IN MALE PROGENY. PATERNAL ENVIRONMENTAL PERTURBATIONS INCLUDING EXPOSURE TO DRUGS OF ABUSE CAN PRODUCE PROFOUND EFFECTS ON THE PHYSIOLOGY AND BEHAVIOR OF OFFSPRING VIA EPIGENETIC MODIFICATIONS. HERE WE SHOW THAT ADULT DRUG-NAIVE MALE OFFSPRING OF COCAINE-EXPOSED SIRES HAVE MEMORY FORMATION DEFICITS AND ASSOCIATED REDUCTIONS IN NMDA RECEPTOR-MEDIATED HIPPOCAMPAL SYNAPTIC PLASTICITY. REDUCED LEVELS OF THE ENDOGENOUS NMDA RECEPTOR CO-AGONIST D-SERINE WERE ACCOMPANIED BY INCREASED EXPRESSION OF THE D-SERINE DEGRADING ENZYME D-AMINO ACID OXIDASE (DAO1) IN THE HIPPOCAMPUS OF COCAINE-SIRED MALE PROGENY. INCREASED DAO1 TRANSCRIPTION WAS ASSOCIATED WITH ENRICHMENT OF PERMISSIVE EPIGENETIC MARKS ON HISTONE PROTEINS IN THE HIPPOCAMPUS OF MALE COCAINE-SIRED PROGENY, SOME OF WHICH WERE ENHANCED NEAR THE DAO1 LOCUS. FINALLY, HIPPOCAMPAL ADMINISTRATION OF D-SERINE REVERSED BOTH THE MEMORY FORMATION AND SYNAPTIC PLASTICITY DEFICITS. COLLECTIVELY, THESE RESULTS DEMONSTRATE THAT PATERNAL COCAINE EXPOSURE PRODUCES EPIGENETIC REMODELING IN THE HIPPOCAMPUS LEADING TO NMDA RECEPTOR-DEPENDENT MEMORY FORMATION AND SYNAPTIC PLASTICITY IMPAIRMENTS ONLY IN MALE PROGENY, WHICH HAS SIGNIFICANT IMPLICATIONS FOR THE MALE DESCENDANTS OF CHRONIC COCAINE USERS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
16  1783  32 EFFECT OF AGOMELATINE ON MEMORY DEFICITS AND HIPPOCAMPAL GENE EXPRESSION INDUCED BY CHRONIC SOCIAL DEFEAT STRESS IN MICE. CHRONIC STRESS IS KNOWN TO INDUCE NOT ONLY ANXIETY AND DEPRESSIVE-LIKE PHENOTYPES IN MICE BUT ALSO COGNITIVE IMPAIRMENTS, FOR WHICH THE ACTION OF CLASSICAL ANTIDEPRESSANT COMPOUNDS REMAINS UNSATISFACTORY. IN THIS CONTEXT, WE INVESTIGATED THE EFFECTS OF CHRONIC SOCIAL DEFEAT STRESS (CSDS) ON ANXIETY-, SOCIAL- AND COGNITIVE-RELATED BEHAVIORS, AS WELL AS HIPPOCAMPAL BDNF, SYNAPTIC PLASTICITY MARKERS (PSD-95, SYNAPTOPHYSIN, SPINOPHILIN, SYNAPSIN I AND MAP-2), AND EPIGENETIC MODIFYING ENZYMES (MYST2, HDAC2, HDAC6, MLL3, KDM5B, DNMT3B, GADD45B) GENE EXPRESSION IN C57BL/6J MICE. CSDS FOR 10 DAYS PROVOKED LONG-LASTING ANXIOUS-LIKE PHENOTYPE IN THE OPEN FIELD AND EPISODIC MEMORY DEFICITS IN THE NOVEL OBJECT RECOGNITION TEST. WHILE TOTAL BDNF MRNA LEVEL WAS UNCHANGED, BDNF EXON IV, MAP-2, HDAC2, HDAC6 AND MLL3 GENE EXPRESSION WAS SIGNIFICANTLY DECREASED IN THE CSDS MOUSE HIPPOCAMPUS. IN CSDS MICE TREATED 3 WEEKS WITH 50 MG/KG/D AGOMELATINE, AN ANTIDEPRESSANT WITH MELATONERGIC RECEPTOR AGONIST AND 5-HT(2C) RECEPTOR ANTAGONIST PROPERTIES, THE ANXIOUS-LIKE PHENOTYPE WAS NOT REVERSED, BUT THE TREATMENT SUCCESSFULLY PREVENTED THE COGNITIVE IMPAIRMENTS AND HIPPOCAMPAL GENE EXPRESSION MODIFICATIONS. ALTOGETHER, THESE DATA EVIDENCED THAT, IN MICE, AGOMELATINE WAS EFFECTIVE IN ALLEVIATING STRESS-INDUCED ALTERED COGNITIVE FUNCTIONS, POSSIBLY THROUGH A MECHANISM INVOLVING BDNF SIGNALING, SYNAPTIC PLASTICITY AND EPIGENETIC REMODELING.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
17  4938  30 PATERNAL NICOTINE ENHANCES FEAR MEMORY, REDUCES NICOTINE ADMINISTRATION, AND ALTERS HIPPOCAMPAL GENETIC AND NEURAL FUNCTION IN OFFSPRING. NICOTINE USE REMAINS HIGHLY PREVALENT WITH TOBACCO AND E-CIGARETTE PRODUCTS CONSUMED WORLDWIDE. HOWEVER, INCREASING EVIDENCE OF TRANSGENERATIONAL EPIGENETIC INHERITANCE SUGGESTS THAT NICOTINE USE MAY ALTER BEHAVIOR AND NEUROBIOLOGY IN SUBSEQUENT GENERATIONS. WE TESTED THE EFFECTS OF CHRONIC PATERNAL NICOTINE EXPOSURE IN C57BL6/J MICE ON FEAR CONDITIONING IN F1 AND F2 OFFSPRING, AS WELL AS CONDITIONED FEAR EXTINCTION AND SPONTANEOUS RECOVERY, NICOTINE SELF-ADMINISTRATION, HIPPOCAMPAL CHOLINERGIC FUNCTIONING, RNA EXPRESSION, AND DNA METHYLATION IN F1 OFFSPRING. PATERNAL NICOTINE EXPOSURE WAS ASSOCIATED WITH ENHANCED CONTEXTUAL AND CUED FEAR CONDITIONING AND SPONTANEOUS RECOVERY OF EXTINGUISHED FEAR MEMORIES. FURTHER, NICOTINE REINFORCEMENT WAS REDUCED IN NICOTINE-SIRED MICE, AS ASSESSED IN A SELF-ADMINISTRATION PARADIGM. THESE BEHAVIORAL PHENOTYPES WERE COUPLED WITH ALTERED RESPONSE TO NICOTINE, UPREGULATED HIPPOCAMPAL NICOTINIC ACETYLCHOLINE RECEPTOR BINDING, REDUCED EVOKED HIPPOCAMPAL CHOLINERGIC CURRENTS, AND ALTERED METHYLATION AND EXPRESSION OF HIPPOCAMPAL GENES RELATED TO NEURAL DEVELOPMENT AND PLASTICITY. GENE EXPRESSION ANALYSIS SUGGESTS MULTIGENERATIONAL EFFECTS ON BROADER GENE NETWORKS POTENTIALLY INVOLVED IN NEUROPLASTICITY AND MENTAL DISORDERS. THE CHANGES IN FEAR CONDITIONING SIMILARLY SUGGEST PHENOTYPES ANALOGOUS TO ANXIETY DISORDERS SIMILAR TO POST-TRAUMATIC STRESS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
18  1004  26 CHRONIC TREATMENT WITH HORMONAL CONTRACEPTIVES ALTERS HIPPOCAMPAL BDNF AND HISTONE H3 POST-TRANSLATIONAL MODIFICATIONS BUT NOT LEARNING AND MEMORY IN FEMALE RATS. HORMONAL CONTRACEPTIVES PREVENT OVULATION WITH SUBSEQUENT REDUCTION IN ENDOGENOUS LEVELS OF ESTRADIOL, PROGESTERONE AND ITS NEUROACTIVE METABOLITE ALLOPREGNANOLONE. THESE NEUROSTEROIDS MODULATE SEVERAL BRAIN FUNCTIONS, INCLUDING NEURONAL PLASTICITY, COGNITION AND MEMORY. WE HYPOTHESIZED THAT HORMONAL CONTRACEPTIVES MIGHT AFFECT SYNAPTIC PLASTICITY, LEARNING AND MEMORY, AS A CONSEQUENCE OF SUPPRESSED ENDOGENOUS HORMONES LEVELS. FEMALE RATS WERE ORALLY TREATED WITH A COMBINATION OF ETHINYL ESTRADIOL (EE, 0.020 MG) AND LEVONORGESTREL (LNG, 0.060 MG) ONCE DAILY FOR FOUR WEEKS. DECREASED HIPPOCAMPAL BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) LEVELS AND ALTERED HISTONE H3 POST-TRANSLATIONAL MODIFICATIONS (PTMS) WERE OBSERVED 14 DAYS AFTER DISCONTINUATION FROM CHRONIC EE-LNG TREATMENT. THESE EFFECTS WERE NOT ACCOMPANIED BY ALTERATIONS IN LONG-TERM PLASTICITY AT GLUTAMATERGIC SYNAPSES, RECOGNITION MEMORY IN THE NOVEL OBJECT AND NOVEL PLACE LOCATION TESTS, OR SPATIAL LEARNING, MEMORY, AND BEHAVIORAL FLEXIBILITY IN THE MORRIS WATER MAZE TEST. THUS, DECREASED BDNF CONTENT DOES NOT AFFECT SYNAPTIC PLASTICITY AND COGNITIVE PERFORMANCE; RATHER IT MIGHT BE RELEVANT FOR THE OCCURRENCE OF CERTAIN PSYCHIATRIC SYMPTOMS, REPORTED BY SOME WOMEN USING HORMONAL CONTRACEPTIVES. THESE RESULTS PROVIDE THE FIRST EVIDENCE OF HIPPOCAMPAL EPIGENETIC CHANGES INDUCED BY HORMONAL CONTRACEPTIVES AND COMPLEMENT PREVIOUS STUDIES ON THE NEUROBIOLOGICAL ACTIONS OF HORMONAL CONTRACEPTIVES; THE FINDING THAT EFFECTS OF CHRONIC EE-LNG TREATMENT ON BDNF CONTENT AND HISTONE PTMS ARE OBSERVED 14 DAYS AFTER DRUG DISCONTINUATION WARRANTS FURTHER INVESTIGATION TO BETTER UNDERSTAND THE IMPLICATIONS OF SUCH LONG-TERM CONSEQUENCES FOR WOMEN'S HEALTH.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
19  5819  24 STRESS CHANGES AMPHETAMINE RESPONSE, D2 RECEPTOR EXPRESSION AND EPIGENETIC REGULATION IN LOW-ANXIETY RATS. THE AIM OF THIS STUDY WAS TO ASSESS THE INFLUENCE OF CHRONIC RESTRAINT STRESS ON AMPHETAMINE (AMPH)-RELATED APPETITIVE 50-KHZ ULTRASONIC VOCALISATIONS (USVS) IN RATS DIFFERING IN FREEZING DURATION IN A CONTEXTUAL FEAR TEST (CFT), I.E. HR (HIGH-ANXIETY RESPONSIVE) AND LR (LOW-ANXIETY RESPONSIVE) RATS. THE LR AND THE HR RATS, PREVIOUSLY EXPOSED TO AN AMPH BINGE EXPERIENCE, DIFFERED IN SENSITIVITY TO AMPH'S REWARDING EFFECTS, MEASURED AS APPETITIVE VOCALISATIONS. MOREOVER, CHRONIC RESTRAINT STRESS ATTENUATED AMPH-RELATED APPETITIVE VOCALISATIONS IN THE LR RATS BUT HAD NO INFLUENCE ON THE HR RATS' BEHAVIOUR. TO SPECIFY, THE RESTRAINT LR RATS VOCALISED APPETITIVELY LESS IN THE AMPH-ASSOCIATED CONTEXT AND AFTER AN AMPH CHALLENGE THAN THE CONTROL LR RATS. THIS PHENOMENON WAS ASSOCIATED WITH A DECREASE IN THE MRNA LEVEL FOR D2 DOPAMINE RECEPTOR IN THE AMYGDALA AND ITS PROTEIN EXPRESSION IN THE BASAL AMYGDALA (BA) AND OPPOSITE CHANGES IN THE NUCLEUS ACCUMBENS (NAC) - AN INCREASE IN THE MRNA LEVEL FOR D2 DOPAMINE RECEPTOR AND ITS PROTEIN EXPRESSION IN THE NAC SHELL, COMPARED TO CONTROL CONDITIONS. MOREOVER, WE OBSERVED THAT CHRONIC RESTRAINT STRESS INFLUENCED EPIGENETIC REGULATION IN THE LR AND THE HR RATS DIFFERENTLY. THE CONTRASTING CHANGES WERE OBSERVED IN THE DENTATE GYRUS (DG) OF THE HIPPOCAMPUS - THE LR RATS PRESENTED A DECREASE, BUT THE HR RATS SHOWED AN INCREASE IN H3K9 TRIMETHYLATION. THE RESTRAINT LR RATS ALSO SHOWED HIGHER MIR-494 AND MIR-34C LEVELS IN THE NAC THAN THE CONTROL LR GROUP. OUR STUDY PROVIDES BEHAVIOURAL AND BIOCHEMICAL DATA CONCERNING THE ROLE OF DIFFERENCES IN FEAR-CONDITIONED RESPONSE IN STRESS VULNERABILITY AND AMPH-ASSOCIATED APPETITIVE BEHAVIOUR. THE LR RATS WERE LESS SENSITIVE TO THE REWARDING EFFECTS OF AMPH WHEN PREVIOUSLY EXPOSED TO CHRONIC STRESS THAT WAS ACCOMPANIED BY CHANGES IN D2 DOPAMINE RECEPTOR EXPRESSION AND EPIGENETIC REGULATION IN MESOLIMBIC AREAS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
20  4944  26 PATERNAL PRECONCEPTION ETHANOL EXPOSURE BLUNTS HYPOTHALAMIC-PITUITARY-ADRENAL AXIS RESPONSIVITY AND STRESS-INDUCED EXCESSIVE FLUID INTAKE IN MALE MICE. A GROWING NUMBER OF ENVIRONMENTAL INSULTS HAVE BEEN SHOWN TO INDUCE EPIGENETIC EFFECTS THAT PERSIST ACROSS GENERATIONS. FOR INSTANCE, PATERNAL PRECONCEPTION EXPOSURES TO ETHANOL OR STRESS HAVE INDEPENDENTLY BEEN SHOWN TO EXERT SUCH INTERGENERATIONAL EFFECTS. SINCE ETHANOL EXPOSURE IS A PHYSIOLOGICAL STRESSOR THAT ACTIVATES THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS, WE HYPOTHESIZED THAT PATERNAL ETHANOL EXPOSURE WOULD IMPACT STRESS RESPONSIVITY OF OFFSPRING. ADULT MALE MICE WERE EXPOSED TO CHRONIC INTERMITTENT VAPOR ETHANOL OR CONTROL CONDITIONS FOR 5 WEEKS BEFORE BEING MATED WITH ETHANOL-NAIVE FEMALES TO PRODUCE ETHANOL (E)- AND CONTROL (C)-SIRED OFFSPRING. ADULT MALE AND FEMALE OFFSPRING WERE TESTED FOR PLASMA CORTICOSTERONE (CORT) LEVELS FOLLOWING ACUTE RESTRAINT STRESS AND THE MALE OFFSPRING WERE FURTHER EXAMINED FOR STRESS-EVOKED 2-BOTTLE CHOICE ETHANOL-DRINKING. PATERNAL ETHANOL EXPOSURE BLUNTED PLASMA CORT LEVELS FOLLOWING ACUTE RESTRAINT STRESS SELECTIVELY IN MALE OFFSPRING; FEMALES WERE UNAFFECTED. IN A STRESS-EVOKED ETHANOL-DRINKING ASSAY, THERE WAS NO EFFECT OF STRESS ON ETHANOL CONSUMPTION. HOWEVER, C-SIRED MALES EXHIBITED INCREASED TOTAL FLUID INTAKE (POLYDIPSIA) IN RESPONSE TO STRESS WHILE E-SIRED MALES WERE RESISTANT TO THIS STRESS-INDUCED PHENOTYPE. TAKEN TOGETHER, THESE DATA SUGGEST THAT PATERNAL ETHANOL EXPOSURE IMPARTS STRESS HYPORESPONSIVITY TO MALE OFFSPRING.	2016