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Lookup NU author(s): Ibtisam Al-Musawi, Bethany Dennis, Dr Gavin ClowryORCiD, Dr Fiona LeBeauORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Introduction: Neuronal hyperexcitability and neuroinflammation are thought to occur at early stages in a range of neurodegenerative diseases. Neuroinflammation, notably activation of microglia, has been identified as a potential prodromal marker of dementia with Lewy bodies (DLB). Using a transgenic mouse model of DLB that over-expresses human mutant (A30P) alpha-synuclein (hα-syn) we have investigated whether early neuroinflammation is evident in the hippocampus in young pre-symptomatic animals.Methods: Previous studies have shown early hyperexcitability in the hippocampal CA3 region in male A30P mice at 2–4 months of age, therefore, in the current study we have immunostained this region for markers of neuronal activity (c-Fos), reactive astrocytes (glial fibrillary acidic protein, GFAP), microglia (ionizing calcium binding adapter protein 1, Iba-1) and reactive microglia (inducible nitric oxide synthase, iNOS).Results: We found an interesting biphasic change in the expression of c-Fos in A30P mice with high expression at 1 month, consistent with early onset of hyperexcitability, but lower expression from 2–4 months in male A30P mice compared to wild-type (WT) controls, possibly indicating chronic hyperexcitability. Neuroinflammation was indicated by significant increases in the % area of GFAP and the number of Iba-1+ cells that expressed iNOS immunoreactivity in the CA3 region in 2–4 months A30P male mice compared to WT controls. A similar increase in % area of GFAP was observed in female A30P mice, however, the Iba-1 count was not different between female WT and A30P mice. In WT mice aged 2–4 months only 4.6% of Iba-1+ cells co-expressed iNOS. In contrast, in age matched A30P mice 87% of cells co-expressed Iba-1 and iNOS. Although there was no difference in GFAP immunoreactivity at 1 month, Iba-1/iNOS co-expression was also increased in a cohort of 1 month old A30P mice.Discussion: Abnormal hα-syn expression in A30P mice caused early changes in network excitability, as indicated by c-Fos expression, and neuroinflammation which might contribute to disease progression.
Author(s): Al-Musawi I, Dennis BH, Clowry GJ, LeBeau FE
Publication type: Article
Publication status: Published
Journal: Frontiers in Dementia
Year: 2024
Volume: 3
Online publication date: 17/06/2024
Acceptance date: 20/05/2024
Date deposited: 05/02/2025
ISSN (electronic): 2813-3919
Publisher: Frontiers Research Foundation
URL: https://doi.org/10.3389/frdem.2024.1404841
DOI: 10.3389/frdem.2024.1404841
Data Access Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
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