Cargando…

Rotenone aggravates PD-like pathology in A53T mutant human α-synuclein transgenic mice in an age-dependent manner

Multiple factors such as genes, environment, and age are involved in developing Parkinson’s disease (PD) pathology. However, how various factors interact to cause PD remains unclear. Here, 3-month and 9-month-old hα-syn(+⁣/−) mice were treated with low-dose rotenone for 2 months to explore the mecha...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, An-Di, Cao, Jia-Xin, Chen, Hai-Chao, Du, Hong-Li, Xi, Xiao-Xia, Sun, Jing, Yin, Jie, Jing, Yu-Hong, Gao, Li-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393581/
https://www.ncbi.nlm.nih.gov/pubmed/36004003
http://dx.doi.org/10.3389/fnagi.2022.842380
Descripción
Sumario:Multiple factors such as genes, environment, and age are involved in developing Parkinson’s disease (PD) pathology. However, how various factors interact to cause PD remains unclear. Here, 3-month and 9-month-old hα-syn(+⁣/−) mice were treated with low-dose rotenone for 2 months to explore the mechanisms that underline the environment–gene–age interaction in the occurrence of PD. We have examined the behavior of mice and the PD-like pathologies of the brain and gut. The present results showed that impairments of the motor function and olfactory function were more serious in old hα-syn(+/–) mice with rotenone than that in young mice. The dopaminergic neuron loss in the SNc is more in old hα-syn(+/–) mice with rotenone than in young mice. Expression of hα-syn(+/–) is increased in the SNc of hα-syn(+/–) mice following rotenone treatment for 2 months. Furthermore, the number of activated microglia cells increased in SNc and accompanied the high expression of inflammatory cytokines, namely, TNF-α and IL-18 in the midbrain of old hα-syn(+/–) mice treated with rotenone. Meanwhile, we found that after treatment with rotenone, hα-syn positive particles deposited in the intestinal wall, intestinal microflora, and T lymphocyte subtypes of Peyer’s patches changed, and intestinal mucosal permeability increased. Moreover, these phenomena were age-dependent. These findings suggested that rotenone aggravated the PD-like pathologies and affected the brain and gut of human α-syn(+/–) transgenic mice in an age-dependent manner.