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Objective: Microtubule (MT) stability in neurons is vital for brain development; instability is associated with neuropsychiatric disorders. The present study examined the effects of social defeat stress (SDS) on MT-regulating proteins and tubulin polymerization. Methods: After 10 days of SDS, defeated mice were separated into susceptible (Sus) and unsusceptible (Uns) groups based on their performance in a social avoidance test. Using extracted brain tissues, we measured the expression levels of α-tubulin, acetylated α-tubulin, tyrosinated α-tubulin, MT-associated protein-2 (MAP2), stathmin (STMN1), phospho stathmin serine 16 (p-STMN1 [Ser16]), phospho stathmin serine 25 (p-STMN1 [Ser25]), phospho stathmin serine 38 (p-STMN1 [Ser38]), stathmin2 (STMN2), phospho stathmin 2 serine 73 (p-STMN2 [Ser73]), 78-kDa glucose-regulated protein (GRP-78), and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) using Western blot assay. The tubulin polymerization rate was also measured. Results: We observed increased and decreased expression of acetylated and tyrosinated α-tubulin, respectively, decreased expression of p-STMN1 (Ser16) and increased expression of p-STMN1 (Ser25), p-STMN2 (Ser73) and GRP-78 and CHOP in the prefrontal cortex and/or hippocampus of defeated mice. A reduced tubulin polymerization rate was observed in the Sus group compared to the Uns and Con groups. Conclusion: Our findings suggest that SDS has detrimental effects on MT stability, and a lower tubulin polymerization rate could be a molecular marker for susceptibility to SDS. [ABSTRACT FROM AUTHOR]

Objective: Understanding complex epigenetic mechanisms is necessary to fully elucidate the effects of antipsychotic drug. This study investigated DNA methylation and mRNA expression levels of dopamine D2 and D1 receptor (Drd2 and Drd1, respectively), nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and stathmin 1 (Stmn1) in brain regions of mice exposed to social defeat stress (SDS) and effects of risperidone on altered methylation and mRNA expression levels induced by SDS. Methods: Following SDS for 10 days, risperidone (0.2 mg/kg) or vehicle was administered to adult mice for 7 days. Brain tissues from the prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY) were processed to measure methylation and mRNA levels of Drd2, Drd1, Nr3c1 and Stmn1 using pyrosequencing and real time-polymerase chain reaction. Results: We found altered methylation status of Nr3c1 and Stmn1 in the HIP and AMY of mice exposed to SDS. These changes were reversed by risperidone treatment. In addition, different methylation patterns of Drd2 and Drd1 in the PFC and AMY between defeated and control mice were identified with risperidone treatment. Conclusion: These findings suggest that risperidone can cause epigenetic changes in Drd2, Drd1, Nr3c1 and Stmn1 in defeated mice. These changes could be epigenetic mechanisms underlying antipsychotic efficacy. [ABSTRACT FROM AUTHOR]