Consequences of brain-derived neurotrophic factor withdrawal in CNS neurons and implications in disease

Abstract

Growth factor withdrawal has been studied across different species and has been shown to have dramatic consequences on cell survival. In the nervous system, withdrawal of nerve growth factor (NGF) from sympathetic and sensory neurons results in substantial neuronal cell death, signifying a requirement for NGF for the survival of neurons in the peripheral nervous system (PNS). In contrast to the PNS, withdrawal of central nervous system (CNS) enriched brain-derived neurotrophic factor (BDNF) has little effect on cell survival but is indispensible for synaptic plasticity. Given that most early events in neuropsychiatric disorders are marked by a loss of synapses, lack of BDNF may thus be an important part of a cascade of events that leads to neuronal degeneration. Here we review reports on the effects of BDNF withdrawal on CNS neurons and discuss the relevance of the loss in disease.

Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury

“…Neurodegeneration in response to stress or injury has been associated with both the induction of neuroinflammatory signals (34)(35)(36)(37) and a corresponding loss of homeostatic prosurvival cues (38)(39)(40)(41). However, the mechanisms by which these activities are coordinated in the CNS remain unclear.…”

Estrogen receptor‐β of microglia underlies sexual differentiation of neuronal protection via ginsenosides in mice brain

“…BDNF is a member of the neurotrophin family that generally promotes neuronal survival. Brains with reduced levels of BDNF become vulnerable to neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease . Although previous reports indicated BDNF is an effective therapeutic substance against bacterial meningitis, the exact mechanism of its efficacy remains unclear .…”

“…Brains with reduced levels of BDNF become vulnerable to neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. 44,45 Although previous reports indicated BDNF is an effective therapeutic substance against bacterial meningitis, the exact mechanism of its efficacy remains unclear. 46 In a previous study, Rb1 activated BDNF through cAMP/protein kinase A (PKA) signaling in a model of Alzheimer's disease.…”

Adeno‐associated virus‐mediated over‐expression of CREB‐regulated transcription coactivator 1 in the hippocampal dentate gyrus ameliorates lipopolysaccharide‐induced depression‐like behaviour in mice

“…; Mariga et al . ). Few studies have assessed the relationship between CRTC1 and VGF expression, although BDNF is closely regulated by CRTC1 in neuropsychiatric disorders.…”