Oral nimodipine treatment has no effect on amyloid pathology or neuritic dystrophy in the 5XFAD mouse model of amyloidosis
| Autor: | Katherine R. Sadleir, Jelena Popovic, Ammaarah Khatri, Robert Vassar |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Physiology Administration Oral Blood Pressure Plaque Amyloid Plant Science Alzheimer's Disease Hippocampus Biochemistry Vascular Medicine Ion Channels Mice Medical Conditions Animal Cells Medicine and Health Sciences Neurons Multidisciplinary Physics Genetically Modified Organisms Brain Neurodegenerative Diseases Animal Models Calcium Channel Blockers Electrophysiology Experimental Organism Systems Neurology Physical Sciences Engineering and Technology Female Anatomy Cellular Types Genetic Engineering Research Article Biotechnology Biophysics Neuroaxonal Dystrophies Neurophysiology Mouse Models Bioengineering Mice Transgenic Research and Analysis Methods Model Organisms Alzheimer Disease Mental Health and Psychiatry Neurites Animals Humans Genetically Modified Animals Biology and Life Sciences Proteins Cell Biology Neuronal Dendrites Plant Pathology Disease Models Animal Cellular Neuroscience Animal Studies Dementia Nimodipine Calcium Channels Neuroscience |
| Zdroj: | PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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