Electroacupuncture restores maternal separation-induced glutamatergic presynaptic deficits of the medial prefrontal cortex in adulthood

Abstract

Maternal separation (MS) serves as a critical model of early life stress (ELS) that can lead to mood disorders, such as depression. Our previous studies suggest that MS may disrupt synaptic transmission in adulthood. While electroacupuncture (EA) has demonstrated antidepressant effects in several animal models of stress-induced depression, it remains unclear whether EA can reverse synaptic transmission deficits caused by ELS. In this study, we examined the effects of EA at Baihui (GV20) and Yintang (GV29) on both behavioural deficits and glutamatergic synaptic transmission in Sprague-Dawley rats subjected to MS. First, we showed that EA effectively alleviated anhedonia and despair-like behaviours. Furthermore, our data indicated that EA restored the decrease in presynaptic glutamate release, as evidenced by changes in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and paired-pulse ratios (PPR). Microdialysis results also suggested that EA elevated extracellular glutamate levels. To explore the underlying mechanisms, we performed Western blot analyses on several proteins involved in glutamatergic synaptic transmission. Notably, we found that EA treatment increased the expression of vesicular glutamate transporters (VGLUT1 and VGLUT2) and vesicle-associated release proteins (SNAP25, Syntaxin-1A, and VAMP2) in the medial prefrontal cortex (mPFC) of MS rats. In contrast, EA did not significantly affect most postsynaptic glutamatergic receptors. These findings underscore the significant impact of EA on glutamatergic synaptic transmission, particularly in restoring presynaptic impairments induced by MS in adulthood.