Evidence for constitutive neural cell proliferation in the adult murine hypothalamus
Evidence for constitutive neural cell proliferation in the adult murine hypothalamus
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DOI：
10.1002/cne.21492
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发表时间：
2007-11-10
影响因子：
2.5
通讯作者：
Flier, Jeffrey S.
中科院分区：
文献类型：
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作者：
Kokoeva, Maia V.;Yin, Huali;Flier, Jeffrey S.
令人信服的证据表明，哺乳动物的大脑能够在整个成年期产生新的神经元。虽然神经发生可以诱导在不同的大脑部位的外源性线索，新的神经元的组成性出生已明确证明在侧脑室的脑室下区（SVZ）和齿状回的颗粒下区（SGZ）。缺乏强有力的证据表明，组成性神经发生发生在成年人大脑的其他地方可能是由于它的独家限制SVZ和SGZ，或者，例如，用于显示在其他大脑部位的新生神经元的方法不足。通过使用脑室内（icv）交付的有丝分裂标志物溴脱氧尿苷（BrdU），我们证明，新的细胞出生连续和大量的成年小鼠下丘脑，这些细胞中的许多出现分化成神经元的双皮质素（Dex）和其他神经元的命运标志物的表达进行评估。与腹膜内（ip）BrdU注射相比，中枢BrdU输注也揭示了睫状神经营养因子（CNTF）对下丘脑细胞增殖的更高倍数诱导。似乎新细胞在整个下丘脑实质中产生，而没有明显的限制特定的神经源性层，如SVZ所示。因此，我们提供的证据表明，成人下丘脑是组成性神经和下丘脑细胞增殖是高度响应有丝分裂原的行动。
Compelling evidence suggests that the mammalian brain is capable of generating new neurons throughout adult life. While neurogenesis can be induced at various brain sites by exogenous cues, constitutive birth of new neurons has been unambiguously demonstrated within the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. The lack of strong evidence that constitutive neurogenesis occurs elsewhere in the adult brain could be due to its exclusive restriction to the SVZ and SGZ or, for instance, to the inadequacy of the methods used to reveal new-born neurons at other brain sites. By using intracerebroventricular (icv) delivery of the mitotic marker bromodeoxyuridine (BrdU) we demonstrate that new cells are born continuously and in substantial numbers in the adult murine hypothalamus and that many of these cells appear to differentiate into neurons as assessed by the expression of doublecortin (Dex) and other neuronal fate markers. As compared to intraperitoneal (ip) BrdU injections, central BrdU infusion also uncovers a higher-fold induction of hypothalamic cell proliferation by ciliary neurotrophic factor (CNTF). It appears that new cells are born throughout the hypothalamic parenchyma without an apparent restriction to a specific neurogenic layer, as seen in the SVZ. Thus, we provide evidence that the adult hypothalamus is constitutively neurogenic and that hypothalamic cell proliferation is highly responsive to mitogen action.