Prophylactic effects of N-acethylcysteine on inflammation-induced depression-like behaviors in mice

Depression, affecting individuals worldwide, is a prevalent mental disease, with an increasing incidence. Numerous studies have been conducted on depression, yet its pathogenesis remains elusive. Recent advancements in research indicate that disturbances in synaptic transmission, synaptic plasticity, and reduced neurotrophic factor expression significantly contribute to depression's pathogenesis. In our study, we utilized adult male C57BL/6J mice. Lipopolysaccharide (LPS) can induce both chronic and acute depression-like symptoms in mice, a widely used model for studying depression associated with inflammation. N-acetylcysteine (NAC) exhibits anti-inflammatory and ameliorative effects on depressive symptoms. This study sought to determine whether NAC use could mitigate inflammatory depressive behavior through the enhancement of synaptic transmission, synaptic plasticity, and increasing levels of brain-derived neurotrophic factor (BDNF). In this study, we discovered that in mice modeled with depression-like symptoms, the expression levels of dendrites, BDNF, and miniature excitatory postsynaptic potential (mEPSC) in glutamatergic neurons, as well as the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPARs) GluA1 and GluA2 subunits, were significantly decreased. These findings suggest an impairment in the synaptic transmission of glutamatergic neurons. Following treatment with NAC, the previously mentioned levels improved, indicating an enhancement in both synaptic transmission and synaptic plasticity. Our results suggest that NAC exerts a protective effect on mouse models of inflammatory depression, potentially through the enhancement of synaptic transmission and plasticity, as well as the restoration of neurotrophic factor expression. These findings offer vital animal experimental evidence supporting NAC's role in mitigating inflammatory depressive behaviors.