Astrocytic water channel aquaporin-4 modulates brain plasticity in both mice and humans: a potential gliogenetic mechanism underlying language-associated learning
- 주제(기타) Biochemistry & Molecular Biology; Neurosciences; Psychiatry
- 설명문(일반) [Woo, J.; Lee, J.; Park, S.; Jung, S-Y; An, H.; Han, Y-E; Feng, L.; Chun, H.; Yoon, B-E; Lee, C. J.] Korea Inst Sci & Technol, Ctr Neural Sci & Funct Connect, Seoul, South Korea; [Woo, J.; Jung, S-Y; Han, Y-E; Lee, C. J.] Univ Sci & Technol, Neurosci Program, Daejeon, South Korea; [Kim, J. E.; Shin, E. Y.; Kang, I.; Lyoo, I. K.] Ewha Womans Univ, Scranton Coll, Dept Brain & Cognit Sci, Seoul, South Korea; [Kim, J. E.; Im, J. J.; Yoon, S.; Lee, S.; Ma, J.; Shin, E. Y.; Kim, B.; Kang, I.; Lyoo, I. K.] Ewha Womans Univ, Ewha Brain Inst, 52 Ewhayeodaegil, Seoul, South Korea; [Im, J. J.; Lee, S.; Ma, J.; Kim, B.] Seoul Natl Univ, Coll Nat Sci, Interdisciplinary Program Neurosci, Seoul, South Korea; [Jeong, H. S.] Catholic Univ Korea, Incheon St Marys Hosp, Dept Radiol, Coll Med, Seoul, South Korea; [An, H.; Dager, S. R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA; [An, H.; Dager, S. R.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA; [Lee, S.] Ewha Womans Univ, Dept Radiol, Coll Med, Seoul, South Korea; [Lee, E. H.] Green Cross Labs, Yongin, South Korea; [Yoon, B-E] Dankook Univ, Dept Nanobiomed Sci, Cheonan, South Korea; [Lyoo, I. K.] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul, South Korea; [Lee, C. J.] Korea Univ, Grad Sch Convergence Technol, KU KIST, Seoul, South Korea; [Lee, J.] Korea Food Res Inst, Div Funct Food Res, Seongnam, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000160201
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/mp.2017.113
초록/요약
The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n = 60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n = 650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n = 45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.
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