Social isolation mediated anxiety like behavior is associated with enhanced expression and regulation of BDNF in the female mouse brain

• Published in: Physiology & behavior 2016-05, Vol.158, p.34-42
• Main Authors: Kumari, Anita, Singh, Padmanabh, Baghel, Meghraj Singh, Thakur, M.K
• Format: Article
• Language: English
• Subjects: Animals; Anxiety; Anxiety - pathology; BDNF; Brain - metabolism; Brain-Derived Neurotrophic Factor - metabolism; Cerebral cortex; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Disease Models, Animal; Exploratory Behavior; Female; Gene Expression Regulation - physiology; HDAC-2; Histone Deacetylase 2 - genetics; Histone Deacetylase 2 - metabolism; Lim Kinases - genetics; Lim Kinases - metabolism; Maze Learning - physiology; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; MiRNA-132; Psychiatry; RNA, Messenger - metabolism; Social isolation; Social Isolation - psychology
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2016.02.032

Abstract Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females. Therefore, in the present study, we have studied the impact of social isolation of young female mice for 8 weeks on the anxiety like behavior and the underlying molecular mechanism. Elevated plus maze and open field test revealed that social isolation caused anxiety like behavior. BDNF, a well-known molecule implicated in the anxiety like behavior, was up-regulated both at the message and protein level in cerebral cortex by social isolation. CREB-1 and CBP, which play a crucial role in BDNF transcription, were up-regulated at mRNA level in cerebral cortex by social isolation. HDAC-2, which negatively regulates BDNF expression, was down-regulated at mRNA and protein level in cerebral cortex by social isolation. Furthermore, BDNF acts in concert with Limk-1, miRNA-132 and miRNA-134 for the regulation of structural and morphological plasticity. Social isolation resulted in up-regulation of Limk-1 mRNA and miRNA-132 expression in the cerebral cortex. MiRNA-134, which inhibits the translation of Limk-1, was decreased in cerebral cortex by social isolation. Taken together, our study suggests that social isolation mediated anxiety like behavior is associated with up-regulation of BDNF expression and concomitant increase in the expression of CBP, CREB-1, Limk-1 and miRNA-132, and decrease in the expression of HDAC-2 and miRNA-134 in the cerebral cortex.