Maternal separation increased memory function and anxiety without effects of environmental enrichment in male rats.

Maternal separation is a detrimental postnatal influence, whereas environmental enrichment is a therapeutic and protective agent. It is unclear if long-term environmental enrichment can compensate for the effects of maternal separation stress on memory-related alterations. This study examined how environmental enrichment affected memory functions, anxiety level, Grin2a, Grin2b, BDNF, and cFos expressions in the maternally separated rats. There are seven groups in this study: control (C), maternal separation+standard cage (MS), maternal separation + enriched cage (MSE), enriched cage (E), the maternal separation that decapitated at postnatal 21 (MS21) and standard cage that decapitated at PN21 (C21) for hormone and gene expression analysis. The maternal separation procedure consisted of postnatal 21 days. Learning and memory performance were determined with the Morris water tank test; anxiety and locomotor activity were examined with the open field and elevated plus-maze test. The expression levels of genes were measured by the RT-PCR method. Blood corticosterone level was evaluated by the ELISA method. Results showed that MS increased memory performance, locomotor activity, and anxiety, but it did not change gene expression levels. An enriched environment did not change the memory performance, locomotor activity, and related gene expression levels. MSE group increased their memory performance, but the anxiety, locomotor activity, and gene expression level did not change. Grin2a, Grin2b, and BDNF gene expression and corticosterone levels increased in the MS21 group. Maternal separation increased memory performance, but it also increased anxiety. Environmental enrichment alone was insufficient to cause alterations in the memory performance.

Hyperthyroidism leads learning and memory impairment possibly via GRIN2B expression alterations.

The hippocampus as an important structure for learning and memory functions contains a high level of thyroid hormone receptors. Although there are numerous studies investigating the effects of thyroid hormones on cognitive dysfunction and psychiatric symptoms, the underlying molecular processes of these disorders have not yet been fully elucidated. In the present study, 24 male adult rats (4 months) were divided into 3 groups: control group, sham group and hyperthyroid group. Hyperthyroid group and sham group were treated with l-thyroxine or saline for 21 days. Each group was exposed to Morris water maze testing (MWMT), measuring their performance in a hidden-platform spatial task. After learning and memory tests, intracardiac blood was taken from the rats for serum thyroxine levels. Following blood collection, the rats were decapitated to isolate hippocampal tissue. GRIN2A, GRIN2B, BDNF, cFOS, Cdk5, cdk5r1 (p35), and cdk5r2 (p39) gene expression were evaluated using quantitative reverse transcriptase-PCR. Serum thyroxine level was found to be higher in hyperthyroid rats than in the control and sham groups. According to our MWMT findings, the memory performance of the hyperthyroid group was significantly impaired compared to the control and sham groups (p < 0.05). In the hippocampus, the GRIN2A gene expression level was decreased in the sham group, and the GRIN2B gene expression level was decreased in the sham and hyperthyroid groups compared to the control group (p < 0.05). There was no significant difference in other genes (p > 0.05). Hyperthyroidism impaired hippocampus-dependent spatial memory. Hyperthyroidism caused decreased level of GRIN2B gene expression in the hippocampus.

Environmental enrichment as a strategy: Attenuates the anxiety and memory impairment in social isolation stress.

BACKGROUND: Social isolation (SI) early in life produces behavioral and cognitive abnormalities. On the contrary, environmental enrichment (EE) offers beneficial effects on brain plasticity and development. This study was designed to examine how EE affects memory functions, anxiety level, and the expression levels of memory/anxiety-related genes such as NR2A, NR2B, BDNF, and cFos in the hippocampus of socially isolated rats. MATERIALS AND METHODS: Wistar albino male rats (n = 40) were separated into the five groups: Standard cage (SC), SI, EE, SI + SC, and SI + EE group. For each group, eight rats were housed, either grouped or isolated, in a standard or 3-week EE, respectively. Morris water maze test (MWMT) was used for measuring the learning and memory function. Elevated plus maze (EPM) and open field (OF) were used for the evaluation of anxiety behavior. Blood corticosterone level was evaluated by the ELISA method. The expression levels of genes were measured by the RT-PCR method. RESULTS: Results showed that EE increased memory performance in the SI group (p < 0.05). SI caused anxiety while EE improved anxiety behavior (p < 0.05). There was no significant difference between the groups in the OF test. Corticosterone levels did not change between groups. BDNF expression level was downregulated in EE and SI + SC compared with the SC group (respectively; p = 0.012; p = 0.011). NR2A, NR2B, and cFos expression levels did not change between groups significantly. CONCLUSIONS: SI impaired memory performance while EE has beneficial effects on memory in socially isolated rats. EE alone was insufficient to cause alterations in the memory performance. The therapeutic effects of EE became strengthened while applied together with stress protocol. Together with improving the effectiveness of memory function, EE has the potential to decrease anxiety behavior. EE seemed to be the reason for decreasing in BDNF.

Mild regular treadmill exercise ameliorated the detrimental effects of acute sleep deprivation on spatial memory.

Vulnerable areas like the hippocampus are sensitive to insults such as sleep deprivation (SD); they are also susceptible to environmental enrichment. Much evidence is accumulating that chronic sleep deprivation causes alterations in the hippocampus that responsible for spatial memory. However, there is conflicting about the differences between acute and chronic SD results. The purpose of this study was to determine the protective effects of mild treadmill exercise on acute SD rats. Four groups were created as control, exercise, sleep deprivation, exercise + sleep deprivation. Multiple platforms method was used to induce REM sleep deprivation (RD) for 48 h. The exercise was applied fivedaysperweekforfour weeks(5 × 4). For the first and second weeks, the length of the exercise was 15 min in two sessions (5 min interval) followed by 15 min in three, 15 min in four sessions. Morris water maze (MWM) was used as a spatial memory test. Gene level was determined by using the qPCR technique. Malondialdehyde (MDA) content in the hippocampus was measured as an extent of peroxidative damage to lipids by using the ELISA method. 48 h RD impaired long-term spatial memory significantly. Mild, regular treadmill exercise ameliorated the detrimental effects of acute sleep deprivation on memory. There was no significant difference in MDA between groups. Hippocampal gene expression did not show any changes in all groups. Lack of correlation between memory impairment and levels of genes in the hippocampus is likely to be related to the differences in behavioral and genetic mechanisms.

Regulating the Regulators in Attention-Deficit/Hyperactivity Disorder: A Genetic Association Study of microRNA Biogenesis Pathways.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent complex psychiatric disorders in children as well as adults. ADHD impacts not only the affected individuals but also their families and social and professional networks. The clinical and diagnostic criteria for ADHD remain imprecise, in part, due to lack of robust biomarkers. ADHD comprises multiple subsets of diseases that present a shared set of downstream clinical findings, while displaying extensive molecular heterogeneity. This calls for innovation in diagnostic strategies that can help establish an ADHD diagnosis unequivocally as well as guiding precision medicine in this common mental health disorder. No study has examined, to the best of our knowledge, the upstream regulation of miRNAs that impact the downstream final ADHD phenotype. The latter focus on putative genetic biomarkers that regulate the regulators and can be tested empirically, for example, through genetic association analyses of the biogenesis pathways for miRNAs that impact the ADHD phenotype. Hence, we report here polymorphic variation in 10 miRNA biogenesis pathway candidate genes, including RNASEN, DGCR8, XPO5, RAN, DICER1, TARBP2, AGO1, AGO2, GEMIN3, and GEMIN4, in a large sample from the Eastern Mediterranean region (N = 355; 191 cases and 164 controls). We found that AGO1 rs595961 was significantly associated with ADHD susceptibility (p < 0.05). While polymorphic variation in other miRNA biogenesis pathway genes did not display a significant association in the present sample, the observations reported herein on miRNA biogenesis variation offer a new avenue of research for innovation in biomarker discovery concerning ADHD and other complex psychiatric diseases with major global health burden.

Possible association of FAS and FASLG polymorphisms with the risk of idiopathic azoospermia in southeast Turkey.

To investigate the association of the genetic variants of FAS/FASLG cell death pathway genes in male infertility, we genotyped the FAS -670A/G, -1377G/A, and FASLG -124A/G single-nucleotide polymorphisms (SNPs) by real-time polymerase chain reaction in 108 infertile men with idiopathic azoospermia and in 125 proven fertile controls. The distribution of genotypes and alleles for SNPs at FAS -1377G/A and FASLG -124A/G loci were determined not to be statistically different between the case and control groups. However, the genotype frequencies of SNPs, FAS -670AA and FAS -670AG, were found to be significantly different between the case and control groups. Whereas the FAS -670AA genotype might be regarded as a higher predisposition for idiopathic azoospermia, FAS -670AG could be interpreted to mean that this genotype provides protection against idiopathic azoospermia. The study of combined genotype and haplotype frequencies has found statistically significant differences between case and control subjects for some combinations. The AA-GG binary genotype for the FAS670 and FAS1377 loci couple, in particular, may have a high degree of predisposition to idiopathic azoospermia. Our results suggest that FAS -670A/G SNP may be a genetic predisposing factor of idiopathic azoospermia among southeastern Anatolian men. Larger studies are needed to verify these findings. Furthermore, our data indicated a possible linkage between the FAS and FASLG genes and idiopathic azoospermia.