👤 Vladimir Naumenko

This study examines neuroanatomical and molecular changes that may be responsible for cognitive impairment in the BTBR mouse model of autism. Compared to control C57Bl/6 mice, BTBR mice exhibited cognitive inflexibility, impaired in an operant learning task. MRI revealed significant brain abnormalities, including reduced cortical volume, smaller ventricles, and asymmetry in the dorsal hippocampus, accompanied by neuronal loss. BTBR mice also showed impaired cerebrospinal fluid dynamics, with reduced production and outflow. Molecular analysis revealed brain region-specific reduction in the expression of Bdnf exons 1, 2, 3, and 4 in untrained BTBR mice. Furthermore, learning induced changes in transcription of Bdnf exons exclusively in BTBR. Elevated proBDNF levels and an increased proBDNF/mature BDNF ratio in the frontal cortex and striatum indicated aberrant BDNF processing. These findings suggest that ASD-related cognitive impairments are linked to a complex of neurodevelopmental abnormalities, potentially connected to disrupted transcription, processing, and signaling of BDNF. Show less

Social context modulates stress physiology and resilience, yet preclinical rat paradigms vary widely in stressor type, timing of social exposure, contact modality, and endpoint definitions. We synthesized rat studies to quantify directional and, where feasible, standardized effect-size evidence for social buffering and to outline translational implications. PubMed, Scopus, and Web of Science were searched (2008-2025) for in vivo rat studies comparing conspecific (pair/group housing or conspecific presence) versus solitary conditions across validated stress and PTSD-like paradigms (e.g., fear conditioning/extinction, CUS/CMS, social defeat, predator threat). Data extraction and reporting followed PRISMA 2020 and SYRCLE guidance. Synthesis followed a two-tier approach: (i) all eligible contrasts were direction-coded as beneficial, neutral/mixed, or detrimental under conspecific conditions based strictly on reported statistical contrasts; and (ii) for domains with sufficient coded contrasts, the proportion of beneficial comparisons was estimated with exact binomial tests and 95% confidence intervals. Standardized mean-difference meta-analysis (Hedges' g; random-effects REML) was conducted only for predefined outcomes with adequate numerical reporting. Forty studies met inclusion criteria, yielding 89 extracted comparisons. Overall, 69/89 comparisons (≈78%) favored conspecific conditions. Domain-level directional syntheses supported predominance of beneficial outcomes for hormonal (0.72; 95% CI 0.50-1.00; p = 0.048) and neurotrophic/plasticity markers (0.89; 95% CI 0.57-1.00; p = 0.020), whereas inflammatory/oxidative outcomes were more variable (0.71; 95% CI 0.39-0.94; p = 0.227). For predefined behavioral endpoints with sufficient data, effect-size pooling showed a large reduction in conditioned fear (Hedges' g = -1.22 [-1.53; -0.91], p < 0.0001). Social buffering is robust at behavioral and neuroendocrine levels and often aligns with neurotrophic/plasticity markers, while peripheral immune/redox readouts are more context-dependent. Show less

Chronic ethanol exposure and genetic factors interact to drive neuroadaptations in alcohol use disorders (AUD). However, the system-level coordination of molecular responses across brain regions remains unclear. The 5-HT system and BDNF are key regulators of neuroplasticity in alcoholism. The 5-HT Show less