title: Aquaporin-4 mediates communication between astrocyte and microglia: Implications of neuroinflammation in experimental Parkinson's disease.
abstract: Aquaporin-4 (AQP4), a water-selective membrane transport protein, is up-regulated in astrocytes in various inflammatory lesions, including Parkinson disease (PD). However, the exact functional roles of AQP4 in neuroinflammation remain unknown. In the present study, we investigated how AQP4 participates in the neuroinflammation of PD using AQP4 knockout (KO) mice and astrocyte-microglial co-cultures. We found that AQP4 KO mice exhibited increased basal and inducible canonical NF-κB activity, and showed significantly enhanced gliosis (astrocytosis and microgliosis) in chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)/probenecid PD models, companying with the increase in the production of IL-1β and TNF-α in the midbrain. Similarly, AQP4 deficiency augmented the activation of the NF-κB pathway and the production of IL-1β and TNF-α in midbrain astrocyte cultures treated with MPP(+) (1-methyl-4-phenylpyridinium). Furthermore, AQP4 deficiency promoted activation of microglial cells in the co-cultured system. Our data provide the first evidence that AQP4 modulates astrocyte-to-microglia communication in neuroinflammation, although its effect on astrocyte inflammatory activation remains to be explored.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: R
authors.initials: R
authors.lastname: Liang
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: F
authors.initials: F
authors.lastname: Fang
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China. Electronic address: Yfan@njmu.edu.cn.
authors.forename: Y
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China; Biomedical Functional Materials Collaborative Innovation Center, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing, Jiangsu 210023, China; Parkinson's Disease Center of Beijing Institute for Brain Disorders, 45 Changchun Street, Beijing 100053, China; Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu 210023, China. Electronic address: Ghu@njmu.edu.cn.
authors.forename: G
authors.initials: G
authors.lastname: Hu
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency* / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020267:MPTP Poisoning / Q000473:pathology*; D008636:Mesencephalon / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D016207:Cytokines; D015259:Dopamine Agents; D005904:Glial Fibrillary Acidic Protein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase
keywords: Parkinson’s disease; aquaporin-4; astrocyte; microglia; neuroinflammation