Neuroprotective effects of lithium in cultured cells and animal models of diseases
Lithium, the major drug used to treat manic depressive illness, robustly protects cultured rat brain neurons from glutamate excitotoxicity mediated by N‐methyl‐D‐aspartate (NMDA) receptors. The lithium neuroprotection against glutamate excitotoxiciy is long‐lasting, requires long‐term pretreatment a...
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Published in | Bipolar disorders Vol. 4; no. 2; pp. 129 - 136 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford UK
Munksgaard International Publishers
01.04.2002
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Subjects | |
Online Access | Get full text |
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Summary: | Lithium, the major drug used to treat manic depressive illness, robustly protects cultured rat brain neurons from glutamate excitotoxicity mediated by N‐methyl‐D‐aspartate (NMDA) receptors. The lithium neuroprotection against glutamate excitotoxiciy is long‐lasting, requires long‐term pretreatment and occurs at therapeutic concentrations of this drug. The neuroprotective mechanisms involve inactivation of NMDA receptors, decreased expression of pro‐apoptotic proteins, p53 and Bax, enhanced expression of the cytoprotective protein, Bcl‐2, and activation of the cell survival kinase, Akt. In addition, lithium pretreatment suppresses glutamate‐induced loss of the activities of Akt, cyclic AMP‐response element binding protein (CREB), c‐Jun – N‐terminal kinase (JNK) and p38 kinase. Lithium also reduces brain damage in animal models of neurodegenerative diseases in which excitotoxicity has been implicated. In the rat model of stroke using middle cerebral artery occlusion, lithium markedly reduces neurologic deficits and decreases brain infarct volume even when administered after the onset of ischemia. In a rat Huntington's disease model, lithium significantly reduces brain lesions resulting from intrastriatal infusion of quinolinic acid, an excitotoxin. Our results suggest that lithium might have utility in the treatment of neurodegenerative disorders in addition to its common use for the treatment of bipolar depressive patients. |
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Bibliography: | ark:/67375/WNG-KHR697N8-W ArticleID:BDI1R179 istex:7CF70D5D2E42C4CC671254070C3BE54A908C6392 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Feature-3 ObjectType-Review-1 |
ISSN: | 1398-5647 1399-5618 |
DOI: | 10.1034/j.1399-5618.2002.01179.x |