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Brain-derived neurotrophic factor (BDNF) is a secreted molecule that plays an important role in the survival and growth of nerve cells. BDNF undergoes complex post-translational processing with cellular proteases. Pro- and mature BDNF forms bind to different receptor types in the brain. BDNF is prominent in the neonatal cerebral cortex. The neonatal period is critical for the proper development of the brain and nervous system. Disruptions in these critical periods can have long-lasting effects on behavior and mental health. Individuals who experience adverse effects in the neonatal period have demonstrated a predisposition to depression and other neurobehavioral disorders. In this work we studied the influence of transient expression (P3–P8) elevation of pro-, mature and mutant forms of BDNF that could not be processed with cellular convertases in the neonatal medial prefrontal cortex (mPFC) on anxiety and depressive-like behavior in adolescents. Elevated expression of mature BDNF (LV-BDNF) increased anxiety and depressive-like behavior at P30. Only immobility in the tail suspension test was increased after expression of mutant BDNF (LV-pBDNF mut). Using our RNA-seq data and available online sn-RNAseq results, we investigated transcriptomic changes in the neonatal mPFC at P8 that underlie subsequent behavioral changes. Mature BDNF expression caused an increased transcriptional response in perivascular stromal cells (PSC) with such genes: Ptgds, Slc6a13, Slc22a6, Bnc2, Slc13a4, Aldh1a2. Based on GWAS data, Ptgds is a candidate gene associated with ADHD and bipolar disorder Pujol-Gualdo et al. (2021); Marín-Méndez et al. (2012); Munkholm et al. (2015). LV-pBDNF mut caused a complete opposite set of transcriptional changes in the PSC compared to LV-BDNF. The observed similar behavioral phenotype after expression of mature and mutant forms of BDNF together with the detected genes related to bipolar disorder underpinned that Bdnf could play a substantial role in the pathogenesis of this neurobehavioral disorder. [ABSTRACT FROM AUTHOR]

Reproductive functions in adult organism are known to be affected by different factors. Effects of social environment at the postnatal ontogenesis attract particular attention since it has deep impact on the development of physiological and emotional state of an individual. Effects of chronic social isolation at different ages on male sexual motivation, testosterone and corticosterone response under conditions of sexual arousal were studied in Wistar rats. After weaning at the 21st [corrected] day of age, rats of one group were isolated for six weeks and after that they were housed in groups of five per cage for ten weeks (Iso3-9). Rats of the second group were housed in groups of five animals per cage till 13 weeks of age, and then they were isolated for six weeks (Iso13-19). Rats of the control group were housed in groups during the experiment. Adult 19 week- old male rats were tested under conditions of sexual arousal. The expression of sexual motivation was estimated as the behavioral activity of a male at the transparent perforated partition separating a receptive female. Isolation of adult male rats reduced the number of approaches to the partition, while the period of time a male spent at the partition was not changed and testosterone response was enhanced as compared to control rats. Chronic social isolation during peri-adolescence reduced sexual motivation and prevented arousal-induced elevation of testosterone. Plasma corticosterone increases at sexual arousal in the two groups of isolated rats did not differ from that in controls. Our results are evidence that social isolation during the post-maturity stage (Iso13-19) did not diminish the manifestation of sexual motivation and hormonal response to a receptive female, while isolation during peri-adolescence attenuated behavioral and hormonal expression of sexual arousal in adult males.