Abstract
ObjectiveStress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders.Materials and MethodsWe examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure.ResultsCysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine.ConclusionsThe animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders.
Highlights
Chronic stress and elevated levels of glucocorticoids have been implicated in psychiatric disorders including anxiety, depression and schizophrenia [1]
Cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment
Brain derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in neuroplasticity [3,4,5], and chronic stress has been known to result in alterations in BDNF/TrkB signaling and changes in neuronal functions [6,7]
Summary
Chronic stress and elevated levels of glucocorticoids have been implicated in psychiatric disorders including anxiety, depression and schizophrenia [1]. The argument that TrkB signaling plays an important role in anxiety and depression has been further strengthened by a recent study which indicated that mice lacking TrkB exhibit increased anxiety-like behaviors [10]. Many studies have shown that the prevalence of anxiety symptoms in schizophrenia and depression patients is higher than in the general population indicating the importance of developing new treatment strategies for this aspect of the disorders [11,12]. Evidence indicates that short-term treatment of mice with cysteamine increases brain as well as serum BDNF levels in rodents [14,15]. A recent study from our laboratory has shown that cysteamine increases TrkB signaling in mouse frontal cortex [15]
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