Protein kinase C activity is associated with prefrontal cortical decline in aging

NEUROBIOLOGY OF AGING

卷:30

Article

Brennan, Avis R.¹  Yuan, Peixiong²  Dickstein, Dara L.³  Rocher, Anne B.³  Hof, Patrick R.³  Manji, Husseini²  Arnsten, Amy F. T.¹ 

[1] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06511 USA

[2] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA

[3] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA

关键词: Prefrontal cortex;    Aging;    Working memory;    Protein kinase C;    Dendritic spines;    Chelerythrine;    Dendrites;   

DOI  :  10.1016/j.neurobiolaging.2007.08.020

来源: Elsevier

【 摘 要 】

Aging is associated with deficiencies in the prefrontal cortex, including working memory impairment and compromised integrity of neuronal dendrites. Although protein kinase C (PKC) is implicated in structural plasticity, and overactivation of PKC results in working memory impairments in young animals, the role of PKC in prefrontal cortical impairments in the aged has not been examined. This study provides the first evidence that PKC activity is associated with prefrontal cortical dysfunction in aging. Pharmacological inhibition of PKC with chelerythrine rescued working memory impairments in aged rats and enhanced working memory in aged rhesus monkeys. Improvement correlated with age, with older monkeys demonstrating a greater degree of improvement following PKC inhibition. Furthermore, PKC activity within the prefrontal cortex was inversely correlated with the length of basal dendrites of prefrontal cortical neurons, as well as with working memory performance in aged rats. Together these findings indicate that PKC is dysregulated in aged animals and that PKC inhibitors may be useful in the treatment of cognitive deficits in the elderly. (C) 2007 Elsevier Inc. All rights reserved.

【 授权许可】

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