AIDSWEEKLY Plus; Monday, December 13, 2004
Staff Medical Writers

According to a study from the United States, "Chronic brain inflammation is the common final pathway in the majority of neurodegenerative diseases and central to this phenomenon is the immunological activation of brain mononuclear phagocyte cells, called microglia.

"This inflammatory mechanism is a central component of HIV-associated dementia (HAD). In the healthy state, there are endogenous signals from neurons and astrocytes, which limit excessive central nervous system (CNS) inflammation. However, the signals controlling this process have not been fully elucidated."

"Studies on the peripheral nervous system suggest that a cholinergic anti-inflammatory pathway regulates systemic inflammatory response by way of acetylcholine acting at the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) found on blood-borne macrophages.

"Recent data from our laboratory indicates that cultured microglial cells also express this same receptor and that microglial anti-inflammatory properties are mediated through it and the p44/42 mitogen-activated protein kinase (MAPK) system," wrote B. Giunta and coworkers.

"Here we report for the first time the creation of an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of 1FN-gamma and the HIV-1 coat glycoprotein, gp120," said investigators.

"Furthermore," Giunta continued, "this activation, as measured by TNF-alpha and nitric oxide (NO) release, is synergistically attenuated through the alpha7 nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine."

"Our findings suggest a novel therapeutic combination to treat or prevent the onset of HAD through this modulation of the microglia inflammatory mechanism," the authors concluded.

Giunta and colleagues published their study in Brain Research Bulletin (Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120. Brain Res Bull. 2004 Aug 30;64(2):165-70.

For more information, contact J. Tan, University S Florida, College Med, Neuroimmunol Laboratory, 3515 E Fletcher Avenue, Tampa, FL 33613, USA.

Publisher contact information for the journal Brain Research Bulletin is: Pergamon-Elsevier Science Ltd., the Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England.

The information in this article comes under the major subject areas of Nicotine, Galantamine, Pharmaceutical & Drug Development, Microglial Activation and HIV-Associated Dementia.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Giunta B, Ehrhart J, Townsend K, et al., "Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120", Brain Res Bull. 2004 Aug 30;64(2):165-70.

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