Glutamate and Neurotrophic Factors in Neuronal Plasticity and Disease

By Mark P. Mattson. Annals of the New York Academy of Sciences, 2008

641 citations recorded by the source corpus.

Glutamate's role as a neurotransmitter at synapses has been known for 40 years, but glutamate has since been shown to regulate neurogenesis, neurite outgrowth, synaptogenesis, and neuron survival in the developing and adult mammalian nervous system. Cell‐surface glutamate receptors are coupled to Ca2+ influx and release from endoplasmic reticulum stores, which causes rapid (kinase‐ and protease‐mediated) and delayed (transcription‐dependent) responses that change the structure and function of neurons. Neurotrophic factors and glutamate interact to regulate developmental and adult neuroplasticity. For example, glutamate stimulates the production of brain‐derived neurotrophic factor (BDNF), which, in turn, modifies neuronal glutamate sensitivity, Ca2+ homeostasis, and plasticity. Neurotrophic factors may modify glutamate signaling directly, by changing the expression of glutamate receptor subunits and Ca2+‐regulating proteins, and also indirectly by inducing the production of antioxidant enzymes, energy‐regulating proteins, and antiapoptotic Bcl‐2 family members. Excessive activation of glutamate receptors, under conditions of oxidative and metabolic stress, may contribute to neuronal dysfunction and degeneration in diseases ranging from stroke and Alzheimer's disease to psychiatric disorders. By enhancing neurotrophic factor signaling, environmental factors such as exercise and dietary energy restriction, and chemicals such as antidepressants may optimize glutamatergic signaling and protect against neurological disorders.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience

View Paper: https://www.semanticscholar.org/paper/82dd1e0485b1229468cfa9759c5dc73974a7e79b

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In Cellular and Molecular Neuroscience

In Developmental Neuroscience

Citations in the corpus

Consensus Paper: Pathological Role of the Cerebellum in Autism (2012, background): “Glutamate is the main excitatory neurotransmitter in the brain and it plays a key role during brain development by regulating multiple processes including neurogenesis, neuronal outgrowth, neuron survival, and synaptogenesis [148].”
Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders (2012, background): “Each of these signaling pathways confer the unique function of BDNF on cells (for review, see (Mattson, 2008; Yoshii and Constantine-Paton, 2010).”
Candidate gene studies of ADHD: a meta-analytic review (2009, neutral): “plasticity (Mattson 2008).”
Stage-Specific Functions of the Small Rho GTPases Cdc42 and Rac1 for Adult Hippocampal Neurogenesis (2013, background): “Miyamoto et al. (2006) have shown that BDNF–TrkB signaling promotes neurite outgrowth via Rac1 in primary hippocampal neurons, raising the possibility that BDNF signaling may similarly recruit Rac1 during later stages of development to regulate dendritic growth of adultborn neurons.”