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Journal Article 2015; 36(5): 490-497 PubMed PMID: 26707050 Citation  Keywords:  Animals, Anxiety, Behavior, Animal, Brain-Derived Neurotrophic Factor:genetics, Estradiol:metabolism, Hippocampus:metabolism, Male, Maze Learning, Memory, Mice, Social Environment,.   

OBJECTIVE: Previous studies reported that environmental enrichment might induce various beneficial effects in the central nervous system. However, the effect of environmental factors on endogenous estrogen level was not investigated. The present study was designed to examine the effect of enriched environment on endogenous estrogen in hippocampus and behavioral outcomes.

METHODS: Behavioural measurements, including open field, elevated plus maze and Morris water maze, were used to evaluate anxiety and learning and memory of the male C57BL/6J mice that were housed in enriched environment for five months. In addition, the estrogen and brain-derived neurotrophic factor (BDNF) expression in the hippocampus were measured.

RESULTS: We found that environmental enrichment decreased anxiety-like behaviors and facilitated spatial learning and memory in male C57BL/6J mice. In addition, the mice raised in enriched environment showed decreased endogenous estrogen levels both in the hippocampus and plasma compared to controls. Furthermore, our results indicated that environmental enrichment up-regulated BDNF mRNA expression level in the hippocampus.

CONCLUSION: In conclusion, environmental enrichment decreased anxiety-like behaviors and facilitated spatial learning and memory in male C57BL/6J mice. Lastly, environmental enrichment up-regulated BDNF mRNA expression level in the hippocampus and decreased plasma estrogen level. The possible mechanism remained to be determined....

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Journal Article 2013; 34(7): 624-634 PubMed PMID: 24464002 Citation  Keywords:  Animals, Animals, Newborn, Brain:drug effects, Brain-Derived Neurotrophic Factor:genetics, Dexamethasone:toxicity, Disease Models, Animal, Drug Interactions, Female, Glucocorticoids:toxicity, Hormone Antagonists:pharmacology, Insulin-Like Growth Factor I:.   

OBJECTIVES: Dexamethasone (Dex) causes neurodegeneration in developing brain. Insulin-like growth factor-I (IGF-I) and -II (IGF-II) are potent neurotrophic and differentiation factors and play key roles in the regulation of growth and development of CNS. Current project evaluated the effects of Dex on IGF-I and -II in developing rat brains.

MATERIAL AND METHODS: Sprague-Dawley rat pups in each litter were divided into vehicle (n=230) or Dex-treated (n=234) groups. Rat pups in the Dex group received one of the 3 different regimens of i.p. Dex: tapering doses (DexTD) on postnatal days (PD) 3 to PD 6 or repeated doses on PD 4 to PD 6 or single dose on PD 6. To quantify the glucocorticoid receptor (GR) blockade effect, rat pups in the DexTD group on PD 3 and 5 received vehicle or RU486 (GR blocker, 60 mg/kg) s.c., twenty minutes prior to Dex treatment.

RESULTS: Dex decreased the gain of body and brain weight while RU486 inhibited these effects. RU486 also prevented the DexTD-induced increase in caspase-3 activity and reduction in IGF-I and -II proteins. Compared to the vehicle, the expression of mRNA of IGF-I and -II decreased at 24 h after DexTD treatment, while RU486 prevented this decrease on IGF-II but not IGF-I.

CONCLUSIONS: Our findings indicate that Dex via GR decreases IGF-I and -II and causes neurodegeneration in the neonatal rat brain....

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Journal Article 2011; 32(3): 246-252 PubMed PMID: 21712773 Citation  Keywords:  Brain-Derived Neurotrophic Factor:genetics, Cell Line, Cells, Cultured, Down-Regulation, Gene Expression Profiling, Gene Silencing, Genome, Human:genetics, Histones:genetics, Humans, Microarray Analysis, Nerve Tissue Proteins:genetics, Neurons:drug effect.   

OBJECTIVE: The regulator of G-protein signaling (RGS) molecules represent a class of proteins that modulate the signaling activity of G-protein coupled receptors. Regulator of G-protein signaling 4 (RGS4) is of particular interest in schizophrenia due to reported downregulation of RGS4 transcripts in schizophrenia as well as a connection between RGS4 and a number of receptors implicated in schizophrenia. The mechanism of RGS4 involvement in the pathophysiology of this illness is not clear.

METHODS: To elucidate thise role of RGS4 in pathophysiology of schizophrenia, we silenced RGS4 using siRNAs in human neuroblastoma cell lines and we studied the effects of differential RGS4 expression by microarray.

RESULTS AND CONCLUSION: The cell lines with downregulated expression of RGS4 showed 67 genes with changed expression (30 underexpressed and 37 overexpressed). We have detected three subgroups of genes which might be implicated in schizophrenia pathophysiology: histone genes, which suggest epigenetic mechanisms of the disease; genes for transcription factors associated with other genes relevant to schizophrenia pathology (BDNF and DISCI1) and a heterogeneous group containing genes for G-proteins (GPR50 and GPR64) and calcium binding proteins....

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Comparative Study 2007; 28(2): 153-158 PubMed PMID: 17435670 Citation  Keywords:  Adolescent, Adult, Anorexia Nervosa:genetics, Brain-Derived Neurotrophic Factor:genetics, Case-Control Studies, Child, Disease Susceptibility, Female, Genotype, Humans, Personality:genetics, Phenotype, Polymorphism, Single Nucleotide, Risk,.   

OBJECTIVES: Polymorphisms in BDNF gene has been proposed, as susceptibility loci for stress-related psychiatric disorders. Several lines of molecular and biochemical evidence point to the role of BDNF in anorexia nervosa (AN). Personality traits may constitute the intermediate phenotypes between genes and vulnerability to AN.

METHODS: BDNF Val66Met and -270C/T polymorphisms were genotyped in 149 patients with AN and 100 healthy control females. Temperamental traits in all subjects were measured with Temperament and Character Inventory. First in case-control analysis, we assessed, if analyzed genotypes confer risk for AN. Next, the association of BDNF gene variants with personality dimensions in patients and control subjects was analyzed.

RESULTS: No significant differences between patients with anorexia nervosa and controls in frequency of genotypes and alleles were observed. AN patients with Met allele showed higher Harm avoidance (Anova F=4.70; p=0.03) than Val/Val homozygotes. AN patients, who carried the T allele of BDNF -270C/T polymorphism showed higher Persistence (Anova F=4.04; p<0.05) and Harm avoidance (Anova F=7.93; p=0.006) than C/C homozygotes, however after correction for multiple testing only the latter association remained statistically significant. No significant relationship between Val/Met 66 genotype and -270C/T genotype with personality was observed in healthy females.

CONCLUSIONS: These results may suggest, that BDNF -270 C/T polymorphism may influence the personality trait associated with higher risk of AN....

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