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Microdose lithium improves behavioral deficits and modulates molecular mechanisms of memory formation in female SAMP-8, a mouse model of accelerated aging.

Title: Microdose lithium improves behavioral deficits and modulates molecular mechanisms of memory formation in female SAMP-8, a mouse model of accelerated aging.
Authors: Arthur Antonio Ruiz Pereira; Alessandra Macedo Pinto; Helena Nascimento Malerba; Mariana Toricelli; Hudson Sousa Buck; Tania Araujo Viel
Source: PLoS ONE, Vol 19, Iss 4, p e0299534 (2024)
Publisher Information: Public Library of Science (PLoS)
Publication Year: 2024
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: Medicine; Science
Description: Alzheimer's disease (AD) is the most common neuronal disorder that leads to the development of dementia. Until nowadays, some therapies may alleviate the symptoms, but there is no pharmacological treatment. Microdosing lithium has been used to modify the pathological characteristics of the disease, with effects in both experimental and clinical conditions. The present work aimed to analyze the effects of this treatment on spatial memory, anxiety, and molecular mechanisms related to long-term memory formation during the aging process of a mouse model of accelerated aging (SAMP-8). Female SAMP-8 showed learning and memory impairments together with disruption of memory mechanisms, neuronal loss, and increased density of senile plaques compared to their natural control strain, the senescence-accelerated mouse resistant (SAMR-1). Chronic treatment with lithium promoted memory maintenance, reduction in anxiety, and maintenance of proteins related to memory formation and neuronal density. The density of senile plaques was also reduced. An increase in the density of gamma-aminobutyric acid A (GABAA) and α7 nicotinic cholinergic receptors was also observed and related to neuroprotection and anxiety reduction. In addition, this microdose of lithium inhibited the activation of glycogen synthase kinase-3beta (GSK-3β), the classical mechanism of lithium cell effects, which could contribute to the preservation of the memory mechanism and reduction in senile plaque formation. This work shows that lithium effects in neuroprotection along the aging process are not related to a unique cellular mechanism but produce multiple effects that slowly protect the brain along the aging process.
Document Type: article in journal/newspaper
Language: English
Relation: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0299534&type=printable; https://doaj.org/toc/1932-6203; https://doaj.org/article/914a6cbb3afd4915a63a6d01ba827472
DOI: 10.1371/journal.pone.0299534
Availability: https://doi.org/10.1371/journal.pone.0299534; https://doaj.org/article/914a6cbb3afd4915a63a6d01ba827472
Accession Number: edsbas.983226B
Database: BASE