Glutamic acid decarboxylase 65 and 67 expression in the lateral septum is up-regulated in association with the postpartum period in mice

Abstract

The postpartum period in mammals undergoes a variety of physiological adaptations, including metabolic, behavioral and neuroendocrine alterations. GABA signaling has been strongly linked to various emotional states, stress responses and offspring protection. However, whether GABA signaling may change in the lateral septum (LS), a core brain region for regulating behavioral, emotional and stress responses in postpartum mice has not previously been examined. In this study, we tested whether the expression of two isoforms of glutamic acid decarboxylase (GAD), GAD65 (GAD2) and GAD67 (GAD1), the rate-limiting enzyme for GABA synthesis, exhibits altered expression in postpartum mice relative to nonmaternal, virgin mice. Using microdissected septal tissue from virgin and age-matched postpartum females, quantitative real-time PCR and Western blotting were carried out to assess GAD mRNA and protein expression, respectively. We found both protein and mRNA expression of GAD67 in the whole septum was up-regulated in postpartum mice. By contrast, no significant difference in the whole septum was observed in GAD65 expression. We then conducted a finer level of analysis using smaller microdissections and found GAD67 to be significantly increased in rostral LS, but not in caudal LS or medial septum (MS). Further, GAD65 mRNA expression in rostral LS, but not in caudal LS or MS was also significantly elevated in postpartum mice. These findings suggest that an increased GABA production in rostral LS of the postpartum mice via elevated GAD65 and GAD67 expression may contribute to multiple alterations in behavioral and emotional states, and responses to stress that occur during the postpartum period. Given that rostral LS contains GABA neurons that are projection neurons or local interneurons, it still needs to be determined whether the function of elevated GABA is for local or distant action or both.