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Publication Abstract Display
Type: Published Abstract
Title: Lower fibroblast growth factor (FGF)-1 levels in cerebrospinal fluid from HIV-infected methamphetamine users are associated with worse neuropsychological performance.
Authors: Letendre SL, Ellis RJ, Woods SP, Everall I, Masliah E, Potter M, Rosario D, Heaton RK, Grant I, and the HNRC Group
Year: 2009
Publication: Journal of NeuroVirology
Volume: 15 Issue: S1 Pages: 48
Abstract:Background: FGFs are expressed in the brain and may play important roles in neuroprotection. FGF-1 is primarily produced by neurons, promotes neuronal survival, and may protect calbindin-immunoreactive interneurons from the neurotoxic effects of HIV-gp120. FGF-2 is produced by astroglial cells and sustains endothelial cell fitness and blood-brain barrier homeostasis. To evaluate the relationships between FGFs and the brain, we measured FGF-1 and FGF-2 in CSF from volunteers differing in HIV status and METH use and compared the results to global neuropsychological (NP) performance. Methods: 169 volunteers enrolled in a NIDA-funded Program (P01 DA12065) that assessed the impact of HIV and METH use on the nervous system. CSF was obtained by lumbar puncture in all volunteers. FGF-1 and FGF-2 were measured by ELISA. METH dependence was determined by the Composite International Diagnostic Interview. NP performance was determined by a comprehensive battery of standardized tests and was summarized by the Global Deficit Score (GDS). Results were analyzed by standard statistical methods, including t-tests, correlations, and multivariable regression. Results: Volunteers were mostly middle-aged (mean 43 years), white (71%) men (87%). 93 (55%) were HIV seropositive and 100 (59%) had a history of METH dependence. 69 (41%) were HCV seropositive. HIV and METH were each associated with lower levels of FGF-1 in CSF (HIV: 1.68 vs. 1.84 log10 pg/mL, p = 0.037; METH: 1.70 vs. 1.84, p = 0.068). Only METH was associated with levels of FGF-2 (0.96 vs. 0.88 log10 pg/mL, p = 0.02). Worse GDS values correlated with lower FGF-1 levels and higher FGF-2 levels (FGF-1: r = − 0.20, p = 0.01; FGF-2: r = 0.14, p = 0.07). Multivariable regression predicting GDS and accounting for HIV, METH, and HCV status confirmed that worse NP performance was associated with lower FGF-1 levels (β = − 0.20, p = 0.006; Model R2 = 0.07, p = 0.01). Conclusions: These findings provide in vivo support that HIV and methamphetamine can alter expression of fibroblast growth factors and that these alterations, particularly reductions in FGF-1, may contribute to the neurocognitive abnormalities that are common in these individuals. The investigational human recombinant FGF-1 that has been developed may provide benefits for HIV− and methamphetamine-associated cognitive impairment.

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