Kokoeva Maia V, Yin Huali, Flier Jeffrey S
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
J Comp Neurol. 2007 Nov 10;505(2):209-20. doi: 10.1002/cne.21492.
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 (Dcx) 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.
有力证据表明，哺乳动物的大脑在成年期能够生成新的神经元。虽然外源性线索可在大脑的不同部位诱导神经发生，但在侧脑室的室下区（SVZ）和齿状回的颗粒下区（SGZ）内，新神经元的组成性生成已得到明确证实。在成年大脑的其他部位缺乏组成性神经发生的有力证据，可能是由于其仅限于SVZ和SGZ，或者例如是由于用于揭示其他脑区新生神经元的方法不够完善。通过脑室内（icv）注射有丝分裂标记物溴脱氧尿苷（BrdU），我们证明成年小鼠下丘脑持续大量生成新细胞，并且通过双皮质素（Dcx）和其他神经元命运标记物的表达评估，这些细胞中的许多似乎分化为神经元。与腹腔内（ip）注射BrdU相比，中枢注射BrdU还发现睫状神经营养因子（CNTF）对下丘脑细胞增殖的诱导倍数更高。与SVZ不同，新细胞似乎在下丘脑实质内各处生成，而没有明显局限于特定的神经发生层。因此，我们提供的证据表明成年下丘脑具有组成性神经发生，并且下丘脑细胞增殖对有丝分裂原作用高度敏感。
