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- 검색키워드
- 저자 : Dager, S R (검색결과 2 건)
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Lyoo, In Kyoon,Dager, Stephen R,Kim, Jieun E,Yoon, Sujung J,Friedman, Seth D,Dunner, David L,Renshaw, Perry F American College of Neuropsychopharmacology 2010 Neuropsychopharmacology Vol.35 No.8
Preclinical studies suggest that lithium may exert neurotrophic effects that counteract pathological processes in the brain of patients with bipolar disorder (BD). To describe and compare the course and magnitude of gray matter volume changes in patients with BD who are treated with lithium or valproic acid (VPA) compared to healthy comparison subjects, and to assess clinical relationships to gray matter volume changes induced by lithium in patients with BD, we conducted longitudinal brain imaging and clinical evaluations of treatment response in 22 mood-stabilizing and antipsychotic medications-naive patients with BD who were randomly assigned to either lithium or VPA treatment after baseline assessment. Fourteen healthy comparison subjects did not take any psychotropic medications during follow-up. Longitudinal data analyses of 93 serial magnetic resonance images revealed lithium-induced increases in gray matter volume, which peaked at week 10–12 and were maintained through 16 weeks of treatment. This increase was associated with positive clinical response. In contrast, VPA-treated patients with BD or healthy comparison subjects did not show gray matter volume changes over time. Results suggest that lithium induces sustained increases in cerebral gray matter volume in patients with BD and that these changes are related to the therapeutic efficacy of lithium.
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Woo, J,Kim, J E,Im, J J,Lee, J,Jeong, H S,Park, S,Jung, S-Y,An, H,Yoon, S,Lim, S M,Lee, S,Ma, J,Shin, E Y,Han, Y-E,Kim, B,Lee, E H,Feng, L,Chun, H,Yoon, B-E,Kang, I,Dager, S R,Lyoo, I K,Lee, C J Macmillan Publishers Limited, part of Springer Nat 2018 Molecular psychiatry Vol.23 No.4
<P>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.</P>
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