Abstract
It is well known that brain-derived neurotrophic factor, BDNF, has an important role in a variety of neuronal aspects, such as differentiation, maturation, and synaptic function in the central nervous system (CNS). BDNF stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), phosphoinositide-3kinase (PI3K), and phospholipase C (PLC)-gamma pathways via activation of tropomyosin receptor kinase B (TrkB), a high affinity receptor for BDNF. Evidence has shown significant contributions of these signaling pathways in neurogenesis and synaptic plasticity in in vivo and in vitro experiments. Importantly, it has been demonstrated that dysfunction of the BDNF/TrkB system is involved in the onset of brain diseases, including neurodegenerative and psychiatric disorders. In this review, we discuss actions of BDNF and related signaling molecules on CNS neurons, and their contributions to the pathophysiology of brain diseases.
Highlights
BDNF, one of the neurotrophic factors, is expressed in a variety of brain regions including the cortex and hippocampus, and exerts beneficial effects in the development, survival, and maintenance of neurons in the central nervous system (CNS)
It is well known that MAPK/ERK, PI3K/Akt, and phospholipase C (PLC)-gamma signaling pathways are stimulated after activation of tropomyosin receptor kinase B (TrkB) receptor by BDNF, and intensive investigations on these signaling have been performed because the BDNF/TrkB-mediated intracellular signals are involved in many neuronal aspects, including neuronal survival and synaptic plasticity [1,2,3,4]
Several lines of studies suggest that the BDNF/TrkB system is involved in hippocampal neurogenesis with distinct effects in dentate gyrus (DG) and subventricular zone (SVZ) in the hippocampus [7]
Summary
BDNF, one of the neurotrophic factors, is expressed in a variety of brain regions including the cortex and hippocampus, and exerts beneficial effects in the development, survival, and maintenance of neurons in the central nervous system (CNS). We mainly focus on the role of mature BDNF through TrkB receptor in neurogenesis and neurodegeneration Concerning neurodegenerative disorders, such as Alzheimer’s disease (AD) that exhibits memory and cognitive deterioration, positive contribution of BDNF in the therapeutic outcomes has been demonstrated because downregulation of neurotrophic signals are considered to be associated with the onset of AD [11]. Cell death of HT22 cells after glutamate exposure was significantly restored by HupA treatment [24] Such a HupA treatment reversed the downregulation of pAkt, p-mammalian target of rapamycin (pmTOR), pp70s6 kinase, and protein levels of both BDNF and pTrkB whereas NGF, NT-3, and NT-4 levels were not recovered, suggesting possible involvement of the BDNF/TrkB system in the effect of HupA [24]. Dou et al compared the levels of 5-HT, dopamine and norepinephrine in four rat groups; control, paroxetine alone (P), zinc + folic acid (ZnY), and zinc + folic acid+ paroxetine (ZnYP), and found that 5-HT, dopamine and norepinephrine, NMDA, and TrkB mRNA levels in the frontal cortex were significantly increased in the ZnY group while no upregulation of BDNF was observed [30]
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