Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120.
Publication/Presentation Date
8-30-2004
Abstract
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. 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 IFN-gamma and the HIV-1 coat glycoprotein, gp120. Furthermore, 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.
Volume
64
Issue
2
First Page
165
Last Page
170
ISSN
0361-9230
Published In/Presented At
Giunta, B., Ehrhart, J., Townsend, K., Sun, N., Vendrame, M., Shytle, D., Tan, J., & Fernandez, F. (2004). Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120. Brain research bulletin, 64(2), 165–170. https://doi.org/10.1016/j.brainresbull.2004.06.008
Disciplines
Medicine and Health Sciences
PubMedID
15342104
Department(s)
Department of Medicine
Document Type
Article