Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment
- *Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10021; ‡Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, Canada M5T 1R8; §Departments of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, 6439 Garner's Ferry Road D40, Columbia, SC 29208; and ¶Department of Psychiatry and Behavioral Neuroscience, McMaster University, Hamilton, ON, Canada, L8N 3Z5
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Contributed by Bruce S. McEwen, January 1, 2004
Abstract
Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.
Footnotes
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↵ † To whom correspondence should be addressed at: Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, Box 165, New York, NY 10021. E-mail: wood{at}alumni.princeton.edu.
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Abbreviations: CORT, corticosterone; CLT, chronic lithium treatment; GLT-1, glial glutamate transporter 1; CREB, cAMP-response element binding; pCREB, phosphorylated CREB; MDD, major depressive disorder; CRS, chronic restraint stress; DG, dentate gyrus.
- Copyright © 2004, The National Academy of Sciences
