PMID: 9185677May 23, 1997Paper

Chloroquine administration in mice increases beta-amyloid immunoreactivity and attenuates kainate-induced blood-brain barrier dysfunction

Neuroscience Letters
J G MielkeG O Ivy

Abstract

The anti-malarial drug chloroquine (CHL) has been reported to cause the accumulation of beta-amyloid peptide containing fragments (fA beta) of the amyloid precursor protein within lysosomes in vitro. However, the significance of this finding with regards to the development of Alzheimer's disease (AD) pathology in vivo is not known. Hence, we investigated the effects of chronic CHL administration in the mouse. Systemically administered CHL caused an astrocytic response and an increase in intracellular A beta immunoreactivity throughout the brain, but no plaque-like pathology. Pharmacological challenge with the excitotoxin kainic acid (KA) revealed a mild proconvulsant effect of CHL pretreatment (P < 0.06). Interestingly, CHL protected the blood-brain barrier from characteristic KA-induced dysfunction. Given the hypothesized involvement of both excitotoxic processes and the vascular system in AD, the observed interactions may assist in elucidating the pathogenesis of AD.

References

Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G L CaporasoP Greengard
Jul 1, 1991·Neurochemical Research·M D NorenbergJ T Neary
Jan 1, 1995·Muscle & Nerve·N MurakamiI Nonaka
Oct 1, 1993·Seminars in Arthritis and Rheumatism·R I Fox
Jan 17, 1996·Annals of the New York Academy of Sciences·W E Van NostrandS M Saporito-Irwin

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Citations

Apr 30, 2010·Journal of Inherited Metabolic Disease·Cinzia Maria Bellettato, Maurizio Scarpa
Oct 23, 2002·Journal of Neurochemistry·Ben A Bahr, Jennifer Bendiske
Sep 4, 2008·Antioxidants & Redox Signaling·Violetta N PivtoraikoJohn J Shacka
Dec 31, 2018·Journal of Alzheimer's Disease : JAD·Liang HuiJonathan D Geiger

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