一项新的研究披露，从健康小鼠胚胎中获取的未成熟的神经元可修复受损的脑部回路并在被移植到成年小鼠体内后令其代谢部分恢复正常；这些成年小鼠因为某种基因缺陷而出现病态性的肥胖。这一原则验证性的发现代表了人们朝着神经元替换疗法这一终极目标前进的漫长道路上向前迈出了一步；研究人员希望神经元替换疗法能够在某一天可用来修复因创伤或疾病而受损的脑组织。
Artur Czupryn及其同事从正常小鼠胚胎的下丘脑中取出未成熟的神经元并将其移植入缺乏瘦素这种激素的某种受体的成年小鼠的下丘脑中；人们已知瘦素可调节体重。研究人员观察到，供体神经元能够分化成4种独特的神经元类型，它们接着会在肥胖小鼠的脑中形成功能性的连接。这些移植的神经元显然恢复了这些肥胖小鼠脑中的瘦素信号传导，因为这些小鼠瘦了下来且它们的代谢开始恢复到了正常水平。尽管研究人员说，神经元替换肯定不是治疗肥胖症的一种实用的方法，但他们的研究为移植处于合适发育阶段的供体神经元可促进恢复脑部控制许多复杂特质的区域的功能提供了证据。（生物谷Bioon.com）
doi:10.1126/science.1209870
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Transplanted Hypothalamic Neurons Restore Leptin Signaling and Ameliorate Obesity in db/db Mice
Artur Czupryn,Yu-Dong Zhou, Xi Chen5, David McNay, Matthew P. Anderson, Jeffrey S. Flier, Jeffrey D. Macklis
Evolutionarily old and conserved homeostatic systems in the brain, including the hypothalamus, are organized into nuclear structures of heterogeneous and diverse neuron populations. To investigate whether such circuits can be functionally reconstituted by synaptic integration of similarly diverse populations of neurons, we generated physically chimeric hypothalami by microtransplanting small numbers of embryonic enhanced green fluorescent protein–expressing, leptin-responsive hypothalamic cells into hypothalami of postnatal leptin receptor–deficient (db/db) mice that develop morbid obesity. Donor neurons differentiated and integrated as four distinct hypothalamic neuron subtypes, formed functional excitatory and inhibitory synapses, partially restored leptin responsiveness, and ameliorated hyperglycemia and obesity in db/db mice. These experiments serve as a proof of concept that transplanted neurons can functionally reconstitute complex neuronal circuitry in the mammalian brain.
