Regulation of neuronal and glial proteins by leptin:: Implications for brain development
Regulation of neuronal and glial proteins by leptin:: Implications for brain development
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DOI：
10.1210/en.140.6.2755
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发表时间：
1999-06-01
期刊：
影响因子：
4.8
通讯作者：
Flier, JS
中科院分区：
文献类型：
--
作者：
Ahima, RS;Bjorbæk, C;Flier, JS
瘦素的完全缺失会导致小鼠和人类严重肥胖，但其生理作用尚未完全确定。早期研究报告称 ob/ob 和 db/db 小鼠脑重量下降且髓鞘形成受损。在这里，我们研究了瘦素缺乏和产后瘦素治疗对大脑重量、广泛的神经元和神经胶质标记物的表达以及运动活动的影响。 ob/ob 和 db/db 小鼠脑重量减轻，突触和神经胶质蛋白的表达模式不成熟，新皮质和海马中的生长相关蛋白升高，突触蛋白 1、突触体相关蛋白 25 和突触短蛋白减少。 ob/ob 和 db/db 小鼠的新皮质、海马和纹状体中髓磷脂碱性蛋白、蛋白脂质蛋白和胶质纤维酸性蛋白的表达也降低。从第 4 周开始的六周瘦素治疗增加了 ob/ob 小鼠的脑重量和蛋白质含量，增加了运动活性，并使生长相关蛋白、突触蛋白-1 和突触体相关蛋白-25 的水平正常化，而不影响突触短蛋白和神经胶质蛋白。与 ob/ob 和 db/db 小鼠相比，肥胖刺鼠 (A(y)/alpha) 小鼠的大脑重量以及突触和神经胶质蛋白的表达正常。这些发现表明，瘦素是成年动物能量储存的外周信号，是小鼠神经系统中正常神经元和神经胶质成熟所必需的。
The complete absence of leptin causes severe obesity in mice and humans, but its physiological roles are incompletely defined. Earlier studies reported decreased brain weight and impaired myelination in ob/ob and db/db mice. Here we have examined the effects of leptin deficiency and postnatal leptin treatment an brain weight, the expression of a broad array of neuronal and glial markers, and locomotor activity. ob/ob and db/db mice have reduced brain weight and an immature pattern of expression of synaptic and glial proteins, with growth-associated protein being elevated in the neocortex and hippocampus, and syntaxin-1, synaptosomal-associated protein-25, and synaptobrevin being decreased. The expression of myelin basic protein, proteolipid protein, and glial fibrillary acidic protein was also decreased in the neocortex, hippocampus, and striatum of ob/ob and db/db mice. Six weeks of leptin treatment initiated at week 4 increased brain weight and protein content, increased locomotor activity, and normalized levels of growth-associated protein, syntaxin-1, and synaptosomal-associated protein-25 in ob/ob mice without affecting synaptobrevin and glial proteins. In contrast with ob/ob and db/db mice, obese agouti (A(y)/alpha) mice had normal brain weight and expression of synaptic and glial proteins. These findings suggest that leptin, a peripheral signal of energy stores in adult animals, is required for normal neuronal and glial maturation in the mouse nervous system.