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Critical roles of astrocytic-CCL2-dependent monocyte infiltration in a DJ-1 knockout mouse model of delayed brain repair.
Choi, Dong-Joo; Yang, Hajie; Gaire, Sushil; Lee, Keon Ah; An, Jiawei; Kim, Byung Gon; Jou, Ilo; Park, Sang Myun; Joe, Eun-Hye.
Afiliación
  • Choi DJ; Department of Pharmacology, National Research Lab of Brain Inflammation, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
  • Yang H; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
  • Gaire S; Department of Pharmacology, National Research Lab of Brain Inflammation, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
  • Lee KA; Department of Brain Science, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
  • An J; Department of Pharmacology, National Research Lab of Brain Inflammation, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
  • Kim BG; Department of Brain Science, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
  • Jou I; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
  • Park SM; Department of Pharmacology, National Research Lab of Brain Inflammation, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
  • Joe EH; Department of Brain Science, Ajou University School of Medicine, Suwon, Kyunggi-do, South Korea.
Glia ; 68(10): 2086-2101, 2020 10.
Article en En | MEDLINE | ID: mdl-32176388
Monocyte-derived macrophages play a role in the repair of the injured brain. We previously reported that a deficiency of the Parkinson's disease (PD)-associated gene DJ-1 delays repair of brain injury produced by stereotaxic injection of ATP, a component of damage-associated molecular patterns. Here, we show that a DJ-1 deficiency attenuates monocyte infiltration into the damaged brain owing to a decrease in C-C motif chemokine ligand 2 (CCL2) expression in astrocytes. Like DJ-1-knockout (KO) mice, CCL2 receptor (CCR2)-KO mice showed defects in monocyte infiltration and delayed recovery of brain injury, as determined by 9.4 T magnetic resonance imaging analysis and immunostaining for tyrosine hydroxylase and glial fibrillary acid protein. Notably, transcriptome analyses showed that genes related to regeneration and synapse formation were similarly downregulated in injured brains of DJ-1-KO and CCR2-KO mice compared with the injured wild-type brain. These results indicate that defective astrogliosis in DJ-1-KO mice is associated with decreased CCL2 expression and attenuated monocyte infiltration, resulting in delayed repair of brain injury. Thus, delayed repair of brain injury could contribute to the development of PD. MAIN POINTS: A DJ-1 deficiency attenuates infiltration of monocytes owing to a decrease in CCL2 expression in astrocytes, which in turn led to delay in repair of brain injury.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Encefálicas / Monocitos / Astrocitos / Quimiocina CCL2 / Proteína Desglicasa DJ-1 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Glia Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesiones Encefálicas / Monocitos / Astrocitos / Quimiocina CCL2 / Proteína Desglicasa DJ-1 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Glia Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Estados Unidos