Trends in Neurosciences
Volume 27, Issue 10, October 2004, Pages 589-594
Journal home page for Trends in Neurosciences

BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders

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Brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT) are known to regulate synaptic plasticity, neurogenesis and neuronal survival in the adult brain. These two signals co-regulate one another such that 5-HT stimulates the expression of BDNF, and BDNF enhances the growth and survival of 5-HT neurons. Impaired 5-HT and BDNF signaling is central to depression and anxiety disorders, but could also play important roles in the pathogenesis of several age-related disorders, including insulin resistance syndrome, Alzheimer's disease and Huntington's disease. Enhancement of BDNF signaling may be a key mechanism whereby cognitive stimulation, exercise, dietary restriction and antidepressant drugs preserve brain function during aging. Behavioral and pharmacological manipulations that enhance 5-HT and BDNF signaling could help promote healthy brain aging.

Section snippets

Roles of BDNF and 5-HT in neuronal plasticity and survival

BDNF, a member of the neurotrophin family, activates a high-affinity cell surface receptor (trkB) that is coupled to activation of phosphatidylinositol-3-kinase and protein kinase B (Akt) (Figure 1). By promoting neurogenesis, synaptic plasticity and cell survival, BDNF plays a pivotal role in the development and plasticity of the brain. During development of the cerebral cortex and hippocampus, BDNF induces the differentiation of neural stem cells into neurons and promotes the survival of

Aging

Aging itself appears to be associated with decreased BDNF signaling in the brain. Amounts of BDNF protein in hippocampal pyramidal neurons and dentate granule cells are decreased during aging in monkeys [22]. Basal levels and maze-training-induced increases in BDNF expression were both significantly lower in hippocampal neurons of rats with age-related impairment in learning and memory than in rats of the same age with normal learning and memory function [23]. The reduced BDNF levels during

Lifestyle and healthy aging: involvement of the dynamic duo

It is well known that diet and exercise influence the risk of major age-related disorders, including cardiovascular and cerebrovascular diseases and diabetes. Data from epidemiological and animal studies indicate that dietary restriction (reduced meal size and/or frequency) 41, 45 and exercise 46, 47 might also promote healthy brain aging. In addition, cognitive stimulation might also reduce the risk of AD [48]. Considerable evidence from animal studies suggests a role for BDNF signaling in the

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