C57BL/6NTac (Bl6) and 129S6/SvEvTac (129Sv) mice display different coping strategies in stressful conditions. Our aim was to evaluate biomarkers related to different adaptation strategies in the brain of male 129Sv and Bl6 mice. We focused on signaling pathways related to the dopamine (DA) system, N-methyl-D-aspartate (NMDA) receptor and epidermal growth factor (EGF) family, shown as the key players in behavioral adaptation. Mice from Bl6 and 129Sv lines were divided into either home cage controls (HCC group) or exposed to repeated motility testing and treated with saline for 11 days (RMT group). Distinct stress responses were reflected in severe body weight loss in 129Sv and the increased exploratory behavior in Bl6 mice. Besides that, amphetamine caused significantly stronger motor stimulation in Bl6. Together with the results from gene expression (particularly Maob), this study supports higher baseline activity of DA system in Bl6. Interestingly, the adaptation is reflected with opposite changes of DA markers in dorsal and ventral striatum. In forebrain, stress increased the gene expressions of Egf-Erbb1 and Nrg1/Nrg2-Erbb4 pathways more clearly in 129Sv, whereas the corresponding proteins were significantly elevated in Bl6. We suggest that not only inhibited activity of the DA system, but also reduced activity of EGF family and NMDA receptor signaling underlies higher susceptibility to stress in 129Sv. Altogether, this study underlines the better suitability of 129Sv for modelling neuropsychiatric disorders than Bl6.

Genetic association studies have implicated neural adhesion-related genes in suicidal behaviour and related psychiatric phenotypes, whereas postmortem brain transcriptomic studies have yielded heterogeneous findings with limited support after multiple-testing correction. We synthesized genetic evidence and examined IgLON expression in bilateral anterior midcingulate cortex (aMCC) samples from 14 suicide and 10 non-suicide donors. RT-qPCR measured eight transcripts from five IgLON genes, including alternative promoter-derived transcripts of LSAMP, NTM and OPCML. We additionally reanalysed published dorsolateral prefrontal cortex (DLPFC) expression data and examined public transcriptomic datasets. The genetic synthesis identified several adhesion-related candidate genes, while exploratory DLPFC reanalysis suggested potentially informative promoter-specific differences in LSAMP expression. In the aMCC, NEGR1 expression was lower in the right hemisphere of suicide donors (suicide/non-suicide ratio = 0.54; FDR-adjusted q = 0.027), but not significantly different in the left. Directional NEGR1 asymmetry also differed between groups (q = 0.026), although this result was sensitive to covariate adjustment and the scope of multiple-testing correction. Blood ethanol adjustment minimally changed effect estimates. No other aMCC transcript or public transcriptomic comparison showed FDR-significant differences. Our findings support anatomically focused, bilateral and transcript-specific investigation of neural adhesion genes in larger, independent cohorts.