Yulyaningsih Ernie, Rudenko Ivan A, Valdearcos Martin, Dahlén Emma, Vagena Eirini, Chan Alvin, Alvarez-Buylla Arturo, Vaisse Christian, Koliwad Suneil K, Xu Allison W
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Eli and Edythe Broad Center of Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell Rep. 2017 Jun 13;19(11):2257-2271. doi: 10.1016/j.celrep.2017.05.060.
Neurons expressing agouti-related protein (AgRP) are essential for feeding. The majority of these neurons are located outside the blood-brain barrier (BBB), allowing them to directly sense circulating metabolic factors. Here, we show that, in adult mice, AgRP neurons outside the BBB (AgRP) were rapidly ablated by peripheral administration of monosodium glutamate (MSG), whereas AgRP neurons inside the BBB and most proopiomelanocortin (POMC) neurons were spared. MSG treatment induced proliferation of tanycytes, the putative hypothalamic neural progenitor cells, but the newly proliferated tanycytes did not become neurons. Intriguingly, AgRP neuronal number increased within a week after MSG treatment, and newly emerging AgRP neurons were derived from post-mitotic cells, including some from the Pomc-expressing cell lineage. Our study reveals that the lack of protection by the BBB renders AgRP vulnerable to lesioning by circulating toxins but that the rapid re-emergence of AgRP is part of a reparative process to maintain energy balance.
表达刺鼠相关蛋白（AgRP）的神经元对进食至关重要。这些神经元中的大多数位于血脑屏障（BBB）之外，使它们能够直接感知循环代谢因子。在这里，我们表明，在成年小鼠中，血脑屏障外的AgRP神经元（AgRP）通过外周注射谷氨酸钠（MSG）被迅速消融，而血脑屏障内的AgRP神经元和大多数阿黑皮素原（POMC）神经元则幸免于难。MSG处理诱导了下丘脑假定神经祖细胞——伸长细胞的增殖，但新增殖的伸长细胞并未变成神经元。有趣的是，MSG处理后一周内AgRP神经元数量增加，新出现的AgRP神经元来源于有丝分裂后的细胞，包括一些来自表达Pomc的细胞谱系的细胞。我们的研究表明，血脑屏障缺乏保护使AgRP易受循环毒素损伤，但AgRP的快速重新出现是维持能量平衡的修复过程的一部分。
