Abstract
Hypercortisolemia is suggested to associate with the onset of depressive symptoms in clinical patients [1–2]. Monoamine oxidases (MAO), the enzymes maintaining the turnover and homeostasis of monoamine neurotransmitter, is up-regulated upon exposure to glucocorticoid in in vitro studies [3–4]. However, the mechanistic involvement of MAO in monoamine deficiency, oxidative stress and neuroinflammation in rodent model of hypercortisolemia is not fully understood. Drug M30 comprises brain selective MAO inhibition and iron-chelating free radical scavenging moieties, and has been demonstrated protective in various neurodegernative disease models [5–6]. This study aims to investigate the neuroprotective effect of M30 against depressive-like behavior induced by chronic corticosterone (CORT) treatment. Adult male Sprague-Dawley rats (220-250g) were given subcutaneous CORT injections with or without concurrent M30 application for 14 days. CORT-treated rats showed significant depressive-like behavior with remarkable increases in plasma corticosterone level. Chronic CORT treatment elicited the increases in MAO activities, serotonin turnover, oxidative stress, neuroinflammation and apoptosis in the hippocampus when compared with the control group. In addition, the cytokine-responsive serotonin and tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO-1) was significantly elevated in the CORT-treated group resulting in serotonin deficiency. Moreover, CORT-treatment impaired the neuroarchitecture of pyramidal CA1 and CA3 neurons. M30 application promisingly abrogated the adverse alterations in the hippocampus and protected the rat against depressive-like behavior provoked by CORT. Therefore, our results provide a strong support that M30 is neuroprotective against depressive-like behavior resulting induced by CORT by antagonizing overactivation of MAO-A that trigger oxidative stress, neuroinflammation, IDO-1 activation, serotonin deficiency and neurodegeneration.
References
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