BDNF–TrkB signaling and neuroprotection in schizophrenia

Abstract

Neurotrophins such as brain-derived neurotropic factor (BDNF), play critical role in neuronal survival, synaptic plasticity and cognitive functions. BDNF is known to mediate its action through various intracellular signaling pathways triggered by activation of tyrosine kinase receptor B (TrkB). Evidence from clinical as well as pre-clinical studies indicate alterations in BDNF signaling in schizophrenia. Moreover, several antipsychotic drugs have time-dependent effects on BDNF levels in both schizophrenia subjects and animal models of schizophrenia. Given the emerging interest in neuroplasticity in schizophrenia understanding the neuroprotective and cell survival roles of BDNF signaling will enhance our knowledge of its diverse effects, which may lead to more effective treatments for schizophrenia. This article will present an overview of recent findings on the role of BDNF signaling in the pathophysiology and treatment of schizophrenia, with a special focus on its neuroprotective effects.

Cardiac over-expression of microRNA-1 induces impairment of cognition in mice

“…These results indicate that in addition to impaired memory, Tg mice may have potential behavioral disturbances, such as depression, mood and anxiety disorders or schizophrenia. Additionally, we found decreased BDNF in the hippocampi of the Tg mice, which is consistent with previous reports of BDNF deregulation in the pathophysiology of fear learning, depression, mood and anxiety disorders and schizophrenia (Adlam and Zaman, 2013;Pandya et al, 2013;Suliman et al, 2013;Dincheva et al, 2014), suggesting that the abnormal cognition of Tg mice may be associated with decreased BDNF in the hippocampus.…”

“…Using three experimental methods, we demonstrated that miR-1 over-expression inhibited BDNF expression, in agreement with previous studies (Brandenburger et al, 2014;Varendi et al, 2014). This finding was further verified by the decreased phosphorylation of CREB, which is a downstream target of BDNF (Minichiello, 2009;Pandya et al, 2013). Notably, it has been reported that p-CREB can activate BDNF transcription by binding to a critical cAMP-responsive element within the Bdnf gene (Tao et al, 1998) and that the reduction of p-CREB then results in a decrease in BDNF.…”

Quetiapine and repetitive transcranial magnetic stimulation ameliorate depression-like behaviors and up-regulate the proliferation of hippocampal-derived neural stem cells in a rat model of depression: The involvement of the BDNF/ERK signal pathway

“…A variety of studies have reported that the BDNF/ERK signaling pathway, which is one of the most important pathways in the nervous system, is closely related to nerve protection and treatments for depression (Mathew et al, 2008;Pandya et al, 2013). After the ERKs are activated, the signals are transferred to the nucleus, and the nuclear transcription factor cyclic AMP response element binding protein (CREB) is then activated to enhance CREB, which up-regulates the expression of BDNF, which in turn, provides feedback regulation to the ERK pathway (Blendy, 2006).…”

TrkB interacts with ErbB4 and regulates NRG1-induced NR2B phosphorylation in cortical neurons before synaptogenesis

“…It is known that binding of BDNF to TrkB elicits various intracellular signaling pathways, including phospholipase Cγ (PLCγ), which mediate the neuroprotective effects of BDNF [13]. Moreover, BDNF enhances NR2B mediated synaptic transmission via activation of TrkB [14].…”