Cysteamine Attenuates the Decreases in TrkB Protein Levels and the Anxiety/Depression-Like Behaviors in Mice Induced by Corticosterone Treatment

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.

Ethanol extracts from Hemerocallis citrina attenuate the decreases of brain-derived neurotrophic factor, TrkB levels in rat induced by corticosterone administration

“…However, there were no significant changes in frontal cortex and hippocampal TrkB mRNA levels after long-term corticosterone or HCE treatment. The results indicated that long-term corticosterone affected the rate of TrkB protein synthesis or degradation but not TrkB mRNA, which was partly consistent with the previous study by Kutiyanawalla et al (2011). As a result, these data suggest HCE-induced antidepressant-like effect is likely through modulation of the BDNF-TrkB neurotrophic signaling pathway.…”

“…Clinical study demonstrates that depression is associated with reduced brain BDNF and its receptor (TrkB) levels and that the reductions can be restored up to the normal value by antidepressant treatment (Thompson et al, 2011). Animal studies have also demonstrated clear evidence that BDNF signaling through TrkB is involved in the mechanisms of action of antidepressant agents (Wang et al, 2010;Kutiyanawalla et al, 2011). BDNF and TrkB levels can therefore be useful markers for antidepressant-like response.…”

Erratum: Transglutaminase 2 overexpression induces depressive-like behavior and impaired TrkB signaling in mice

“…Chronic corticosterone treatment has been shown to induce a depressive-like phenotype and a decrease in TrkB protein levels in mouse PFC 9 . We did not find any significant change in fluid consumption rate in mice following corticosterone administration for 7 weeks ( Supplementary Fig.…”

Macranthol promotes hippocampal neuronal proliferation in mice via BDNF–TrkB–PI3K/Akt signaling pathway

“…Brain-derived neurotrophic factor (BDNF), one of the important neurotrophic factors, has also been implicated in the pathophysiology of major depression and the mechanism of antidepressant treatment (Duman and Voleti, 2012;Hayley and Anisman, 2013). A growing number of studies have demonstrated clear evidence that BDNF signaling through tropomyosin-related kinase B (TrkB) is involved in the mechanisms of antidepressants in animal models (Kutiyanawalla et al, 2011;Yi et al, 2014a), and clinical study also demonstrates that depression is associated with reduced brain BDNF and its receptor, TrkB levels and that the reductions can be reversed to the normal value with antidepressant treatment (Thompson Ray et al, 2011).…”