Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer

Abstract

Brain-derived neurotrophic factor (BDNF) is one of the most distributed and extensively studied neurotrophins in the mammalian brain. BDNF signals through the tropomycin receptor kinase B (TrkB) and the low affinity p75 neurotrophin receptor (p75NTR). BDNF plays an important role in proper growth, development, and plasticity of glutamatergic and GABAergic synapses and through modulation of neuronal differentiation, it influences serotonergic and dopaminergic neurotransmission. BDNF acts as paracrine and autocrine factor, on both pre-synaptic and post-synaptic target sites. It is crucial in the transformation of synaptic activity into long-term synaptic memories. BDNF is considered an instructive mediator of functional and structural plasticity in the central nervous system (CNS), influencing dendritic spines and, at least in the hippocampus, the adult neurogenesis. Changes in the rate of adult neurogenesis and in spine density can influence several forms of learning and memory and can contribute to depression-like behaviors. The possible roles of BDNF in neuronal plasticity highlighted in this review focus on the effect of antidepressant therapies on BDNF-mediated plasticity. Moreover, we will review data that illustrate the role of BDNF as a potent protective factor that is able to confer protection against neurodegeneration, in particular in Alzheimer’s disease. Finally, we will give evidence of how the involvement of BDNF in the pathogenesis of brain glioblastoma has emerged, thus opening new avenues for the treatment of this deadly cancer.

Handgrip Strength and Depression Among Older Chinese Inpatients: A Cross-Sectional Study

“…Some studies have found myokines, such as brain-derived neurotrophic factor and irisin, through specific signaling pathways to mediate depression symptoms. 9 , 41 Finally, low handgrip strength influences depression through psychosocial mechanisms. Older adults with low handgrip strength usually experience a decline in physical ability and function, which limits their opportunities to participate in outdoor activities, decreasing possible social contact with other people.…”

Antioxidant and Neuroprotective Activity of Extra Virgin Olive Oil Extracts Obtained from Quercetano Cultivar Trees Grown in Different Areas of the Tuscany Region (Italy)

“…BDNF interacts with tropomyosin-related kinase B (TrkB) and p75 cellular receptors and supports maintenance of normal brain function, neurite outgrowth and synaptic plasticity [ 73 , 74 ]. Several lines of evidence indicate BDNF levels play an important role in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease (AD) [ 75 ]. In the brain of AD patients or aged subjects, BDNF expression levels are lower compared with healthy subjects [ 76 , 77 ].…”

“…In animal models of Parkinson’s disease (PD), BDNF enhances the survival of dopaminergic neurons, improves dopaminergic neurotransmission and motor performance [ 86 ]. Moreover, as previously underlined, neurotrophins prevent cell death and support neuronal proliferation and maturation enhancing both growth and function of affected neurons in Alzheimer’s disease (AD) and PD [ 75 , 86 , 87 ]. Despite the under threshold of BDNF z -score value derived by IPA, both transcript and protein expression analysis by PCR and WB confirmed a significant increase of the neurotrophic factor expression in SH-SY5Y cells treated with the hill extract.…”

Concepts of Neuroinflammation and Their Relationship With Impaired Mitochondrial Functions in Bipolar Disorder

“…As reported above, both cross-sectional and longitudinal studies have indicated that administration of antidepressants and mood stabilizers such as lithium and valproate has normalized BDNF, promoting so, a neuroprotection stress-induced, protecting the cells through anti-apoptotic pathways activation (Colucci-D’Amato et al, 2020 ). It can also increase the gray matter promoting neurogenesis in the subventricular zone of the lateral ventricle and subgranular zone of the hippocampal dentate gyrus, and improve cognitive functions such as learning and memory, both in animal and human studies (Sassi et al, 2002 ; Gould, 2007 ; Kempton et al, 2008 ; Machado-Vieira et al, 2009 ; Hashimoto, 2010 ; Corena-McLeod et al, 2013 ; Yu and Greenberg, 2016 ).…”