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Author Meeker, Rick B. ♦ Boles, Jeramiah C. ♦ Robertson, Kevin R. ♦ Hall, Colin D.
Source SpringerLink
Content type Text
Publisher Springer-Verlag
File Format PDF
Copyright Year ©2005
Language English
Subject Domain (in DDC) Technology ♦ Medicine & health
Subject Keyword AIDS ♦ calcium transporter ♦ dementia ♦ microglia ♦ neurons ♦ sodium/calcium exchanger ♦ Neurosciences ♦ Virology ♦ Infectious Diseases ♦ Immunology ♦ Neurology
Abstract Neurologic decline associated with penetration of human immunodeficiency virus type 1 (HIV-1) into the central nervous system is thought to be due, in large part, to inflammation and local secretion of neurotoxic substances. To examine the cellular processes that mediate neurotoxicity in vivo, the authors evaluated the ability of neurons to maintain intracellular calcium homeostasis in the presence of toxic cerebrospinal fluid (CSF) (CSF$_{tox}$) collected from a subset of HIV-infected individuals. Exposure of rat neural cultures to CSF$_{tox}$ resulted in a gradual increase in intracellular calcium in neurons (+63%), microglia (+251%), and astrocytes (+52%). Pretreatment of neural cultures with CSF$_{tox}$ resulted in an exaggerated calcium response to a brief pulse of glutamate and a >90% suppression of the rate of recovery of intracellular calcium. Attempts to model the deficit using inhibitors of calcium transport across endoplasmic reticulum, mitochondrial, or plasma membrane indicated that blockade of the plasma membrane sodium/calcium exchanger was best able to reproduce the deficits seen during exposure to CSF$_{tox}$. Because the inability of cells to maintain calcium homeostasis would lead to exaggerated responses from a wide variety of stimuli, therapeutics designed to facilitate calcium transport from the cell may provide more comprehensive and effective intervention than strategies targeted to specific receptor pathways.
ISSN 13550284
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2005-01-01
Publisher Place New York
e-ISSN 15382443
Journal Journal of NeuroVirology
Volume Number 11
Issue Number 2
Page Count 13
Starting Page 144
Ending Page 156


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Source: SpringerLink