Short-Term Plasticity of Gray Matter Associated with Leptin Deficiency and Replacement
Short-Term Plasticity of Gray Matter Associated with Leptin Deficiency and Replacement
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DOI：
10.1210/jc.2011-0314
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发表时间：
2011-08-01
影响因子：
5.8
通讯作者：
Licinio, Julio
中科院分区：
文献类型：
--
作者：
London, Edythe D.;Berman, Steven M.;Licinio, Julio
背景：瘦素影响神经发生、神经元生长和活力。我们之前报道过，补充瘦素增加了前扣带回（ACG）、小脑和顶叶下小叶的灰质（GM）浓度，这些区域也与食物摄入有关。目的：本研究的目的是报道瘦素补充不同状态下脑结构的变化。设计：我们进行了一项非随机试验。环境和患者：我们研究了三名由于瘦素基因突变而患有先天性瘦素缺乏症的成年人。干预：患者接受重组甲硫基人瘦素治疗，每年11- 36天暂停治疗，然后在3年内恢复治疗。主要结局指标：GM浓度（通过磁共振扫描体素形态学分析）与体重指数（BMI）和瘦素补充相关。结果：每年停止补充瘦素数周可增加BMI，并逆转瘦素在小脑和ACG中的原始作用。ACG的变化与瘦素通过增加BMI介导的间接影响一致。在瘦素受体最密集的小脑中，转基因变化似乎是瘦素的直接影响。瘦素恢复在短期内没有导致GM的恢复，但确实导致左侧丘脑后半部分，特别是枕核的GM意外增加。结论：这些发现首次在体内证明了瘦素对人脑形态具有显著的可塑性、可逆性和区域特异性作用。他们认为瘦素可能在调节可塑性依赖的大脑功能方面具有治疗价值。[J] .中华内分泌杂志，2011,31(5):555 - 557。
Context: Leptin affects neurogenesis, neuronal growth, and viability. We previously reported that leptin supplementation increased gray matter (GM) concentration in the anterior cingulate gyrus (ACG), cerebellum, and inferior parietal lobule, areas that are also involved in food intake.Objective: The aim of this study was to report the changes in brain structure at different states of leptin supplementation.Design: We conducted a nonrandomized trial.Setting and Patients: We studied three adults with congenital leptin deficiency due to a mutation in the leptin gene.Intervention: Patients received treatment with recombinant methionyl human leptin, with annual 11- to 36-d periods of treatment withholding followed by treatment restoration over 3 yr.Main Outcome Measures: GM concentration (by voxel-based morphometry analysis of magnetic resonance scans) was correlated with body mass index (BMI) and leptin supplementation.Results: Annually withholding leptin supplementation for several weeks increased BMI and reversed the original effects of leptin in the cerebellum and ACG. The changes in the ACG were consistent with an indirect effect of leptin mediated through increased BMI. In the cerebellum, where leptin receptors are most dense, GM changes appeared to be direct effects of leptin. Leptin restoration did not lead to recovery of GM in the short term but did lead to an unexpected GM increase in the posterior half of the left thalamus, particularly the pulvinar nucleus.Conclusion: These findings provide the first in vivo evidence of remarkably plastic, reversible, and regionally specific effects of leptin on human brain morphology. They suggest that leptin may have therapeutic value in modulating plasticity-dependent brain functions. (J Clin Endocrinol Metab 96: E1212-E1220, 2011)