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Publication : Hypersensitivity of aquaporin 4-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine and astrocytic modulation.

First Author  Fan Y Year  2008
Journal  Neurobiol Aging Volume  29
Issue  8 Pages  1226-36
PubMed ID  17353068 Mgi Jnum  J:140917
Mgi Id  MGI:3814812 Doi  10.1016/j.neurobiolaging.2007.02.015
Citation  Fan Y, et al. (2008) Hypersensitivity of aquaporin 4-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine and astrocytic modulation. Neurobiol Aging 29(8):1226-36
abstractText  Aquaporin 4 (AQP4) is a predominant water channel protein in mammalian brains, which is localized in the astrocyte plasma membrane. AQP4 has gained much attraction due to its involvement in the physiopathology of cerebral disorders including stroke, tumor, infection, hydrocephalus, epilepsy, and traumatic brain injury. But there is almost no evidence whether abnormal AQP4 levels are associated with degenerative diseases, such as Parkinson's disease (PD). In our studies, we established PD animal models by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to test the hypothesis that abnormal AQP4 expression is involved in the pathophysiology of this disease. We show that mutant mice lacking AQP4 were significantly more prone to MPTP-induced neurotoxicity than their wild-type littermates. Furthermore, after administration of MPTP, astroglial proliferation and GDNF protein synthesis were inhibited by AQP4 deficiency. This study demonstrates that AQP4 is important in the MPTP neurotoxic process and indicates that the therapeutic strategy targeted to astrocytic modulation with AQP4 may offer a great potential for the development of new treatment for PD.
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