Neuronal Plasticity, Stress and Depression: Involvement of the Cytoskeletal Microtubular System?

Authors: Bianchi, M.; Hagan, J. J.; Heidbreder, C. A.

Source: Current Drug Targets-CNS & Neurological Disorders, Volume 4, Number 5, October 2005 , pp. 597-611(15)

Publisher: Bentham Science Publishers

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Abstract:

In susceptible individuals, stressors can increase the risk of onset of depression and recent brain imaging studies have shown morphometric alterations in the limbic system of patients affected by depression. The volume loss observed in the hippocampus of depressed individuals suggests a possible involvement of structural neuronal plasticity in the pathogenesis of depression. Stressful conditions in animals can result in impaired structural neuronal plasticity in the hippocampus, characterised by retraction of apical dendrites and decreased neurogenesis. The intrinsic dynamic instability of the cytoskeletal microtubular system is essential for neuronal remodelling and plasticity. We have recently shown that both acute and chronic stress decrease microtubular dynamics in the rat hippocampus. Other authors have demonstrated that proteins functionally involved in the regulation of microtubule dynamics can be altered by stress in the rodent hippocampus. Furthermore, the existence of a link between stress-induced microtubular changes and depression is further strengthened by evidence showing that both acute and chronic treatment with antidepressant drugs can affect the expression of microtubular proteins. The present review will introduce a growing body of evidence suggesting that stress-induced alterations in neuronal plasticity might be considered the final result of activation and/or inhibition of molecular cascades regulating the dynamics of the microtubular system. In addition, the prospect of targeting microtubules as a pharmacotherapeutic approach to treat mood disorders will be discussed.

Keywords: hippocampus; stress; mood disorders; neuronal plasticity; microtubular system; tubulin; microtubular associated proteins; antidepressant drugs

Document Type: Review article

DOI: http://dx.doi.org/10.2174/156800705774322012

Affiliations: 1: Institute of Neuroscience, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.

Publication date: 2005-10-01

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CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

Neuronal Plasticity, Stress and Depression: Involvement of the Cytoskeletal Microtubular System?

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