Sex and Age Differences in a Progressive Synucleinopathy Mouse Model.

Autor: Lamontagne-Proulx J; Centre de Recherche du CHU de Québec, Axe Neurosciences, T2-32, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.; Laboratoire International Associé OptiNutriBrain (NutriNeuro France-INAF Canada), Québec, QC G1V 0A6, Canada., Coulombe K; Centre de Recherche du CHU de Québec, Axe Neurosciences, T2-32, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada., Morissette M; Centre de Recherche du CHU de Québec, Axe Neurosciences, T2-32, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada., Rieux M; Centre de Recherche du CHU de Québec, Axe Neurosciences, T2-32, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada., Calon F; Centre de Recherche du CHU de Québec, Axe Neurosciences, T2-32, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.; Laboratoire International Associé OptiNutriBrain (NutriNeuro France-INAF Canada), Québec, QC G1V 0A6, Canada.; Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, 2440, Boulevard Hochelaga, Bureau 1705, Québec, QC G1V 0A6, Canada., Di Paolo T; Centre de Recherche du CHU de Québec, Axe Neurosciences, T2-32, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.; Laboratoire International Associé OptiNutriBrain (NutriNeuro France-INAF Canada), Québec, QC G1V 0A6, Canada., Soulet D; Centre de Recherche du CHU de Québec, Axe Neurosciences, T2-32, 2705, Boulevard Laurier, Québec, QC G1V 4G2, Canada.; Laboratoire International Associé OptiNutriBrain (NutriNeuro France-INAF Canada), Québec, QC G1V 0A6, Canada.; Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, 2440, Boulevard Hochelaga, Bureau 1705, Québec, QC G1V 0A6, Canada.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2023 Jun 11; Vol. 13 (6). Date of Electronic Publication: 2023 Jun 11.
DOI: 10.3390/biom13060977
Abstrakt: The mutation and overexpression of the alpha-synuclein protein (αSyn), described as synucleinopathy, is associated with Parkinson's disease (PD)-like pathologies. A higher prevalence of PD is documented for men versus women, suggesting female hormones' implication in slowing PD progression. The nigrostriatal dopamine (DA) neurons in rodent males are more vulnerable to toxins than those in females. The effect of biological sex on synucleinopathy remains poorly described and was investigated using mice knocked out for murine αSyn (SNCA-/-) and also overexpressing human αSyn (SNCA-OVX) compared to wildtype (WT) mice. All the mice showed decreased locomotor activity with age, and more abruptly in the male than in the female SNCA-OVX mice; anxiety-like behavior increased with age. The SNCA-OVX mice had an age-dependent accumulation of αSyn. Older age was associated with the loss of nigral DA neurons and decreased striatal DA contents. The astrogliosis, microgliosis, and cytokine concentrations increased with aging. More abrupt nigrostriatal DA decreases and increased microgliosis were observed in the male SNCA-OVX mice. Human αSyn overexpression and murine αSyn knockout resulted in behavioral dysfunctions, while only human αSyn overexpression was toxic to DA neurons. At 18 months, neuroprotection was lost in the female SNCA-OVX mice, with a likely loss of estrus cycles. In conclusion, sex-dependent αSyn toxicity was observed, affecting the male mice more significantly.
Databáze: MEDLINE
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