CHCHD10 S59L/+ mouse model: Behavioral and neuropathological features of frontotemporal dementia.

Autor: Genin EC; Université Côte d'Azur (UniCa), Institute for Research on Cancer and Aging (IRCAN), UMR CNRS 7284/INSERM U1081, Centre Hospitalier Universitaire (CHU) de Nice, Nice, France., di Borgo PP; Université Côte d'Azur (UniCa), Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, Inserm, Sophia Antipolis, Valbonne, France., Lorivel T; Université Côte d'Azur (UniCa), Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, Inserm, Sophia Antipolis, Valbonne, France., Hugues S; E-Phy-Science, Bioparc, 2400 Route des Colles, Sophia Antipolis 06410, Biot, France., Farinelli M; E-Phy-Science, Bioparc, 2400 Route des Colles, Sophia Antipolis 06410, Biot, France., Mauri-Crouzet A; Université Côte d'Azur (UniCa), Institute for Research on Cancer and Aging (IRCAN), UMR CNRS 7284/INSERM U1081, Centre Hospitalier Universitaire (CHU) de Nice, Nice, France., Lespinasse F; Université Côte d'Azur (UniCa), Institute for Research on Cancer and Aging (IRCAN), UMR CNRS 7284/INSERM U1081, Centre Hospitalier Universitaire (CHU) de Nice, Nice, France., Godin L; Université Côte d'Azur (UniCa), Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, Inserm, Sophia Antipolis, Valbonne, France., Paquis-Flucklinger V; Université Côte d'Azur (UniCa), Institute for Research on Cancer and Aging (IRCAN), UMR CNRS 7284/INSERM U1081, Centre Hospitalier Universitaire (CHU) de Nice, Nice, France. Electronic address: paquis@unice.fr., Petit-Paitel A; Université Côte d'Azur (UniCa), Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), CNRS UMR7275, Inserm, Sophia Antipolis, Valbonne, France. Electronic address: paitel@ipmc.cnrs.fr.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2024 Jun 01; Vol. 195, pp. 106498. Date of Electronic Publication: 2024 Apr 05.
DOI: 10.1016/j.nbd.2024.106498
Abstrakt: CHCHD10-related disease causes a spectrum of clinical presentations including mitochondrial myopathy, cardiomyopathy, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We generated a knock-in mouse model bearing the p.Ser59Leu (S59L) CHCHD10 variant. Chchd10 S59L/+ mice have been shown to phenotypically replicate the disorders observed in patients: myopathy with mtDNA instability, cardiomyopathy and typical ALS features (protein aggregation, neuromuscular junction degeneration and spinal motor neuron loss). Here, we conducted a comprehensive behavioral, electrophysiological and neuropathological assessment of Chchd10 S59L/+ mice. These animals show impaired learning and memory capacities with reduced long-term potentiation (LTP) measured at the Perforant Pathway-Dentate Gyrus (PP-DG) synapses. In the hippocampus of Chchd10 S59L/+ mice, neuropathological studies show the involvement of protein aggregates, activation of the integrated stress response (ISR) and neuroinflammation in the degenerative process. These findings contribute to decipher mechanisms associated with CHCHD10 variants linking mitochondrial dysfunction and neuronal death. They also validate the Chchd10 S59L/+ mice as a relevant model for FTD, which can be used for preclinical studies to test new therapeutic strategies for this devastating disease.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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