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Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis.

Authors :
Sadleir KR
Popovic J
Khatri A
Vassar R
Source :
PloS one [PLoS One] 2022 Feb 02; Vol. 17 (2), pp. e0263332. Date of Electronic Publication: 2022 Feb 02 (Print Publication: 2022).
Publication Year :
2022

Abstract

Dysregulation of calcium homeostasis has been hypothesized to play a role in Alzheimer's disease (AD) pathogenesis. Increased calcium levels can impair axonal transport, disrupt synaptic transmission, and ultimately lead to cell death. Given the potential role of calcium dyshomeostasis in AD, there is interest in testing the ability of already approved drugs targeting various calcium channels to affect amyloid pathology and other aspects of disease. The objective of this study was to test the effects of FDA-approved L-type calcium channel antagonist nimodipine on amyloid accumulation and dystrophic neurite formation in 5XFAD mice, a mouse model of amyloid pathology. 5XFAD transgenic mice and non-transgenic littermates were treated with vehicle or nimodipine-containing chow from two to eight months of age, then brains were harvested and amyloid pathology assessed by immunoblot and immunofluorescence microscopy analyses. Nimodipine was well tolerated and crossed the blood brain barrier, as expected, but there was no effect on Aβ accumulation or on the relative amount of neuritic dystrophy, as assessed by either immunoblot, dot blot or immunofluorescence imaging of Aβ42 and dystrophic neurite marker LAMP1. While we conclude that nimodipine treatment is not likely to improve amyloid pathology or decrease neuritic dystrophy in AD, it is worth noting that nimodipine did not worsen the phenotype suggesting its use is safe in AD patients.<br />Competing Interests: The authors have declared that no competing interests exist.

Details

Language :
English
ISSN :
1932-6203
Volume :
17
Issue :
2
Database :
MEDLINE
Journal :
PloS one
Publication Type :
Academic Journal
Accession number :
35108319
Full Text :
https://doi.org/10.1371/journal.pone.0263332