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Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease
As the population ages, a high prevalence of multimorbidity will affect the way physicians need to think about drug interactions. With microglia’s important involvement in the pathology and progression of Alzheimer’s disease (AD), understanding whether systemically administered drugs intended for ot...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572937/ https://www.ncbi.nlm.nih.gov/pubmed/37833922 http://dx.doi.org/10.3390/ijms241914474 |
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author | Boboc, Ianis Kevyn Stefan Cojocaru, Alexandru Nedelea, Gabriel Catalin, Bogdan Bogdan, Maria Calina, Daniela |
author_facet | Boboc, Ianis Kevyn Stefan Cojocaru, Alexandru Nedelea, Gabriel Catalin, Bogdan Bogdan, Maria Calina, Daniela |
author_sort | Boboc, Ianis Kevyn Stefan |
collection | PubMed |
description | As the population ages, a high prevalence of multimorbidity will affect the way physicians need to think about drug interactions. With microglia’s important involvement in the pathology and progression of Alzheimer’s disease (AD), understanding whether systemically administered drugs intended for other affections could impact microglia function, already impacted by the presence of beta-amyloid, is important. The aim of this study was to evaluate morphological changes of microglia, using in vivo 2-photon laser scanning microscopy, in a murine model of AD under systemic administration of sodium or calcium ion channel blockers in order to establish potential effects that these drugs might have on microglia under neuro-inflammatory conditions. A total of 30 mice (age 14–16 weeks, weight 20–25 g) were used, with 25 APP randomly divided into three groups. The remaining animals were CX(3)CR(1)(GFP/G)(FP) male mice (n = 5) used as WT controls. After baseline behavior testing, all animals received daily intraperitoneal injections for 30 days according to the assigned group [WT (n = 5), Control (n = 5), Carbamazepine (n = 10), and Verapamil (n = 10)]. The results showed that the Verapamil treatment improved short-term memory and enhanced exploratory behavior in APP mice. The Carbamazepine treatment also improved short-term memory but did not elicit significant changes in anxiety-related behavior. Both Verapamil and Carbamazepine reduced the surveillance speed of microglia processes and changed microglia morphology in the cortex compared to the Control group. Due to their complex molecular machinery, microglia are potentially affected by drugs that do not target them specifically, and, as such, investigating these interactions could prove beneficial in our management of neurodegenerative pathologies. |
format | Online Article Text |
id | pubmed-10572937 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105729372023-10-14 Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease Boboc, Ianis Kevyn Stefan Cojocaru, Alexandru Nedelea, Gabriel Catalin, Bogdan Bogdan, Maria Calina, Daniela Int J Mol Sci Article As the population ages, a high prevalence of multimorbidity will affect the way physicians need to think about drug interactions. With microglia’s important involvement in the pathology and progression of Alzheimer’s disease (AD), understanding whether systemically administered drugs intended for other affections could impact microglia function, already impacted by the presence of beta-amyloid, is important. The aim of this study was to evaluate morphological changes of microglia, using in vivo 2-photon laser scanning microscopy, in a murine model of AD under systemic administration of sodium or calcium ion channel blockers in order to establish potential effects that these drugs might have on microglia under neuro-inflammatory conditions. A total of 30 mice (age 14–16 weeks, weight 20–25 g) were used, with 25 APP randomly divided into three groups. The remaining animals were CX(3)CR(1)(GFP/G)(FP) male mice (n = 5) used as WT controls. After baseline behavior testing, all animals received daily intraperitoneal injections for 30 days according to the assigned group [WT (n = 5), Control (n = 5), Carbamazepine (n = 10), and Verapamil (n = 10)]. The results showed that the Verapamil treatment improved short-term memory and enhanced exploratory behavior in APP mice. The Carbamazepine treatment also improved short-term memory but did not elicit significant changes in anxiety-related behavior. Both Verapamil and Carbamazepine reduced the surveillance speed of microglia processes and changed microglia morphology in the cortex compared to the Control group. Due to their complex molecular machinery, microglia are potentially affected by drugs that do not target them specifically, and, as such, investigating these interactions could prove beneficial in our management of neurodegenerative pathologies. MDPI 2023-09-23 /pmc/articles/PMC10572937/ /pubmed/37833922 http://dx.doi.org/10.3390/ijms241914474 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Boboc, Ianis Kevyn Stefan Cojocaru, Alexandru Nedelea, Gabriel Catalin, Bogdan Bogdan, Maria Calina, Daniela Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease |
title | Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease |
title_full | Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease |
title_fullStr | Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease |
title_full_unstemmed | Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease |
title_short | Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease |
title_sort | chronic administration of ion channel blockers impact microglia morphology and function in a murine model of alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572937/ https://www.ncbi.nlm.nih.gov/pubmed/37833922 http://dx.doi.org/10.3390/ijms241914474 |
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