Abstract
Progression of neuronal deterioration within specific brain regions is considered as one of the principal bases for the development of major depressive disorders. Therefore, protects and promotes the maintaining of normal structure and function of neurons might be a potential therapeutic strategy in the treatment of depression. Here, we report that the antioxidant, N-acetylcysteine (NAC), inhibited neuronal injury through its capacity to reduce oxidative stress and exerted antidepressant effects. Specifically, we show that antioxidant enzyme activity was significantly decreased in the hippocampal CA1 region of depressive rats, while treatment with NAC (300 mg/kg, i.p.) produced neuroprotective effects against mitochondrial oxidative stress injuries and oxidative DNA damage in CA1 neurons of these rats. Moreover, NAC treatment alleviated neuronal injury resulting from neuroinflammation and apoptosis in depressed rats, effects that were associated with reductions in dendritic spine atrophy, and synapse deficits. These effects appear to involve a down-regulation of p38 mitogen-activated protein kinase (MAPK)-JNK signaling along with an up-regulation of ERK signaling within the hippocampal CA1 region. Moreover, this NAC treatment significantly ameliorated depression-like behaviors as indicated by performance in the sucrose preference and forced swim tests (FST). Taken together, these results reveal the potential involvement of oxidative stress in the generation of depression. And, the antidepressant-like effects exerted by NAC may involve reductions in this oxidative stress that can result in neuronal deterioration. Such neuroprotective effects of NAC may indicate a potential therapeutic strategy for the treatment of stress-related depression.
Highlights
Major depression disorder (MDD) is considered a prevalent psychiatric condition usually resulting from stressful stimuli which produce neuronal abnormalities and cell death within specific brain regions (Stockmeier et al, 2004; Oh et al, 2012)
These results reveal that the oxidative stress induced by chronic unpredictable mild stress (CUMS) produced a deterioration of the neuronal structure, while NAC treatment provided neuroprotective effects against these changes
These results suggest that the initial increase in oxidative damage within the CA1 region, resulting from CUMS-exposure may be one of the triggers of inflammation and apoptosis, subsequently leading to neuronal injury
Summary
Major depression disorder (MDD) is considered a prevalent psychiatric condition usually resulting from stressful stimuli which produce neuronal abnormalities and cell death within specific brain regions (Stockmeier et al, 2004; Oh et al, 2012). Antioxidant treatment inhibits ROS-induced biochemical and anatomical changes in the ventral tegmental area (VTA), one of the major regions involved in the generation of MDD (Ibi et al, 2017), while overexpression of superoxide dismutase (SOD) has been reported to protect against glucocorticoidinduced depression-like behavioral phenotypes (Uchihara et al, 2016). Identification of the effects and mechanisms underlying the oxidative stress as associated with the progression of depression represents critical information required for the development of more effective treatments for this disorder
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