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A P arkinson's disease gene, DJ ‐1, repairs brain injury through S ox9 stabilization and astrogliosis
Author(s) -
Choi DongJoo,
Eun JinHwa,
Kim Byung Gon,
Jou Ilo,
Park Sang Myun,
Joe EunHye
Publication year - 2018
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23258
Subject(s) - astrogliosis , gliosis , astrocyte , neurotrophic factors , neurodegeneration , neurite , biology , immunostaining , neuroscience , brain derived neurotrophic factor , traumatic brain injury , striatum , tyrosine hydroxylase , microbiology and biotechnology , pathology , medicine , immunology , central nervous system , dopamine , immunohistochemistry , disease , biochemistry , receptor , in vitro , psychiatry
Defects in repair of damaged brain accumulate injury and contribute to slow‐developing neurodegeneration. Here, we report that a deficiency of DJ‐1, a Parkinson's disease (PD) gene, delays repair of brain injury due to destabilization of Sox9, a positive regulator of astrogliosis. Stereotaxic injection of ATP into the brain striatum produces similar size of acute injury in wild‐type and DJ‐1‐knockout (KO) mice. However, recovery of the injury is delayed in KO mice, which is confirmed by 9.4T magnetic resonance imaging and tyrosine hydroxylase immunostaining. DJ‐1 regulates neurite outgrowth from damaged neurons in a non‐cell autonomous manner. In DJ‐1 KO brains and astrocytes, Sox9 protein levels are decreased due to enhanced ubiquitination, resulting in defects in astrogliosis and glial cell‐derived neurotrophic factor/ brain‐derived neurotrophic factor expression in injured brain and astrocytes. These results indicate that DJ‐1 deficiency causes defects in astrocyte‐mediated repair of brain damage, which may contribute to the development of PD.