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

John G. Mielke; M. Paul Murphy; Jonathan Maritz; Karen M. Bengualid; Gwen O. Ivy

doi:10.1016/S0304-3940(97)00340-6

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

John G. Mielke, M. Paul Murphy, Jonathan Maritz, Karen M. Bengualid, Gwen O. Ivy

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

The anti-malarial drug chloroquine (CHL) has been reported to cause the accumulation of β-amyloid peptide containing fragments (fAβ) 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 Aβ 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.

Original language	English
Pages (from-to)	169-172
Number of pages	4
Journal	Neuroscience Letters
Volume	227
Issue number	3
DOIs	https://doi.org/10.1016/S0304-3940(97)00340-6
State	Published - May 23 1997

Bibliographical note

Funding Information:
We would like to thank Drs. Yasuo Ihara and Sayeeda Zain for the kind gifts of the Aβ antibody and the original group of transgenic animals, respectively. This work was supported by a grant from NSERC Canada (to G.O.I.).

Keywords

Alzheimer's disease
Astrocytes
Blood-brain barrier
Chloroquine
Kainic acid
β-amyloid

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0304-3940(97)00340-6

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title = "Chloroquine administration in mice increases β-amyloid immunoreactivity and attenuates kainate-induced blood-brain barrier dysfunction",

abstract = "The anti-malarial drug chloroquine (CHL) has been reported to cause the accumulation of β-amyloid peptide containing fragments (fAβ) 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 Aβ 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.",

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author = "Mielke, {John G.} and Murphy, {M. Paul} and Jonathan Maritz and Bengualid, {Karen M.} and {O. Ivy}, Gwen",

note = "Funding Information: We would like to thank Drs. Yasuo Ihara and Sayeeda Zain for the kind gifts of the Aβ antibody and the original group of transgenic animals, respectively. This work was supported by a grant from NSERC Canada (to G.O.I.).",

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AU - Maritz, Jonathan

AU - Bengualid, Karen M.

AU - O. Ivy, Gwen

N1 - Funding Information: We would like to thank Drs. Yasuo Ihara and Sayeeda Zain for the kind gifts of the Aβ antibody and the original group of transgenic animals, respectively. This work was supported by a grant from NSERC Canada (to G.O.I.).

PY - 1997/5/23

Y1 - 1997/5/23

N2 - The anti-malarial drug chloroquine (CHL) has been reported to cause the accumulation of β-amyloid peptide containing fragments (fAβ) 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 Aβ 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.

AB - The anti-malarial drug chloroquine (CHL) has been reported to cause the accumulation of β-amyloid peptide containing fragments (fAβ) 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 Aβ 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.

KW - Alzheimer's disease

KW - Astrocytes

KW - Blood-brain barrier

KW - Chloroquine

KW - Kainic acid

KW - β-amyloid

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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