Open AccessAquaporin‐4 deficiency reduces TGF‐β1 in mouse midbrains and exacerbates pathology in experimental Parkinson's disease
Author(s) -
Xue Xue,
Zhang Weiwei,
Zhu Jifeng,
Chen Xiaojun,
Zhou Sha,
Xu Zhipeng,
Hu Gang,
Su Chuan
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14147
Subject(s) - mptp , aquaporin 4 , microglia , astrocyte , immune system , cytokine , inflammation , parkinson's disease , tyrosine hydroxylase , medicine , transforming growth factor , neuroprotection , immunology , endocrinology , disease , dopamine , central nervous system
Aquaporin‐4 (AQP4), the main water‐selective membrane transport protein in the brain, is localized to the astrocyte plasma membrane. Following the establishment of a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced Parkinson's disease (PD) model, AQP4‐deficient (AQP4 −/− ) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH + )‐positive neurons than did wild‐type AQP4 (AQP4 +/+ ) controls. Microglia are the most important immune cells that mediate immune inflammation in PD. However, recently, few studies have reported why AQP4 deficiency results in more severe hypermicrogliosis and neuronal damage after MPTP treatment. In this study, transforming growth factor‐β1 (TGF‐β1), a key suppressive cytokine in PD onset and development, failed to increase in the midbrain and peripheral blood of AQP4 −/− mice after MPTP treatment. Furthermore, the lower level of TGF‐β1 in AQP4 −/− mice partially resulted from impairment of its generation by astrocytes; reduced TGF‐β1 may partially contribute to the uncontrolled microglial inflammatory responses and subsequent severe loss of TH + neurons in AQP4 −/− mice after MPTP treatment. Our study provides not only a better understanding of both aetiological and pathogenical factors implicated in the neurodegenerative mechanism of PD but also a possible approach to developing new treatments for PD via intervention in AQP4‐mediated immune regulation.