一項新的研究披露,，從健康小鼠胚胎中獲取的未成熟的神經(jīng)元可修復受損的腦部回路并在被移植到成年小鼠體內(nèi)后令其代謝部分恢復正常,；這些成年小鼠因為某種基因缺陷而出現(xiàn)病態(tài)性的肥胖。這一原則驗證性的發(fā)現(xiàn)代表了人們朝著神經(jīng)元替換療法這一終極目標前進的漫長道路上向前邁出了一步,；研究人員希望神經(jīng)元替換療法能夠在某一天可用來修復因創(chuàng)傷或疾病而受損的腦組織,。
Artur Czupryn及其同事從正常小鼠胚胎的下丘腦中取出未成熟的神經(jīng)元并將其移植入缺乏瘦素這種激素的某種受體的成年小鼠的下丘腦中,；人們已知瘦素可調(diào)節(jié)體重。研究人員觀察到,，供體神經(jīng)元能夠分化成4種獨特的神經(jīng)元類型,，它們接著會在肥胖小鼠的腦中形成功能性的連接。這些移植的神經(jīng)元顯然恢復了這些肥胖小鼠腦中的瘦素信號傳導,，因為這些小鼠瘦了下來且它們的代謝開始恢復到了正常水平,。盡管研究人員說，神經(jīng)元替換肯定不是治療肥胖癥的一種實用的方法,，但他們的研究為移植處于合適發(fā)育階段的供體神經(jīng)元可促進恢復腦部控制許多復雜特質(zhì)的區(qū)域的功能提供了證據(jù),。（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.
