Behavioral and electrophysiological evidence for a neuroprotective role of aquaporin-4 in the 5xFAD transgenic mice model.

Autor: Abe Y; Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. yoabe@a6.keio.jp.; Center for Water Biology & Medicine, Keio University Global Research Institute, Mita, Tokyo, 108-8345, Japan. yoabe@a6.keio.jp., Ikegawa N; Department of Information and Communication Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo, 102-8554, Japan., Yoshida K; Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Sinjuku-ku, Tokyo, 160-8582, Japan., Muramatsu K; Department of Neuropathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Hattori S; Division of System Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan., Kawai K; Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan., Murakami M; Department of Information and Communication Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo, 102-8554, Japan., Tanaka T; Department of Information and Communication Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo, 102-8554, Japan., Goda W; Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan., Goto M; Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan., Yamamoto T; Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan., Hashimoto T; Department of Neuropathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Yamada K; Department of Neuropathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Shibata T; Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.; Division of Pharmacology, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo, 105-8512, Japan., Misawa H; Division of Pharmacology, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo, 105-8512, Japan., Mimura M; Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Sinjuku-ku, Tokyo, 160-8582, Japan., Tanaka KF; Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Sinjuku-ku, Tokyo, 160-8582, Japan., Miyakawa T; Division of System Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan., Iwatsubo T; Department of Neuropathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan., Hata JI; Central Institute for Experimental Animals (CIEA), 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan., Niikura T; Department of Information and Communication Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo, 102-8554, Japan., Yasui M; Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. myasui@a3.keio.jp.; Center for Water Biology & Medicine, Keio University Global Research Institute, Mita, Tokyo, 108-8345, Japan. myasui@a3.keio.jp.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2020 May 12; Vol. 8 (1), pp. 67. Date of Electronic Publication: 2020 May 12.
DOI: 10.1186/s40478-020-00936-3
Abstrakt: Aquaporin-4 (AQP4) has been suggested to be involved in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), which may be due to the modulation of neuroinflammation or the impairment of interstitial fluid bulk flow system in the central nervous system. Here, we show an age-dependent impairment of several behavioral outcomes in 5xFAD AQP4 null mice. Twenty-four-hour video recordings and computational analyses of their movement revealed that the nighttime motion of AQP4-deficient 5xFAD mice was progressively reduced between 20 and 36 weeks of age, with a sharp deterioration occurring between 30 and 32 weeks. This reduction in nighttime motion was accompanied by motor dysfunction and epileptiform neuronal activities, demonstrated by increased abnormal spikes by electroencephalography. In addition, all AQP4-deficient 5xFAD mice exhibited convulsions at least once during the period of the analysis. Interestingly, despite such obvious phenotypes, parenchymal amyloid β (Aβ) deposition, reactive astrocytosis, and activated microgliosis surrounding amyloid plaques were unchanged in the AQP4-deficient 5xFAD mice relative to 5xFAD mice. Taken together, our data indicate that AQP4 deficiency greatly accelerates an age-dependent deterioration of neuronal function in 5xFAD mice associated with epileptiform neuronal activity without significantly altering Aβ deposition or neuroinflammation in this mouse model. We therefore propose that there exists another pathophysiological phase in AD which follows amyloid plaque deposition and neuroinflammation and is sensitive to AQP4 deficiency.
Databáze: MEDLINE
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