Constitutive cell proliferation and neurogenesis in the organum vasculosum lamina terminalis and subfornical organ of adult rats

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Suijian Zhou, Olena Makashova, Pierre-Marie Chevillard, Vanessa Josey, Banruo Li, Masha Prager-Khoutorsky
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Abstract

Neurogenesis continues throughout adulthood in the subventricular zone, hippocampal subgranular zone, and the hypothalamic median eminence (ME) and the adjacent medio-basal hypothalamus. The ME is one of the circumventricular organs (CVO), which are specialized brain areas characterized by an incomplete blood–brain barrier and, thus, are involved in mediating communication between the central nervous system and the periphery. Additional CVOs include the organum vasculosum laminae terminalis (OVLT) and the subfornical organs (SFO). Previous studies have demonstrated that the ME contains neural stem cells (NSCs) capable of generating new neurons and glia in the adult brain. However, it remains unclear whether the OVLT and SFO also contain proliferating cells, the identity of these cells, and their ability to differentiate into mature neurons. Here we show that glial and mural subtypes exhibit NSC characteristics, expressing the endogenous mitotic maker Ki67, and incorporating the exogenous mitotic marker BrdU in the OVLT and SFO of adult rats. Glial cells constitutively proliferating in the SFO comprise NG2 glia, while in the OVLT, both NG2 glia and tanycytes appear to constitute the NSC pool. Furthermore, pericytes, which are mural cells associated with capillaries, also contribute to the pool of cells constitutively proliferating in the OVLT and SFO of adult rats. In addition to these glial and mural cells, a fraction of NSCs containing proliferation markers Ki67 and BrdU also expresses the early postmitotic neuronal marker doublecortin, suggesting that these CVOs comprise newborn neurons. Notably, these neurons can differentiate and express the mature neuronal marker NeuN. These findings establish the sensory CVOs OVLT and SFO as additional neurogenic niches, where the generation of new neurons and glia persists in the adult brain.

Abstract Image

Abstract Image

成年大鼠血管内膜终末器官和角膜下器官的连续细胞增殖和神经发生。
在整个成年期,脑室下区、海马晶状体下区、下丘脑正中突起(ME)和邻近的下丘脑基底内侧都有神经发生。下丘脑正中突是脑室周围器官(CVO)之一,这些特殊脑区的特点是血脑屏障不完整,因此参与中枢神经系统与外周之间的沟通。其他CVO包括末端血管层器官(OVLT)和角膜下器官(SFO)。先前的研究表明,ME含有神经干细胞(NSCs),能够在成人大脑中生成新的神经元和胶质细胞。然而,OVLT和SFO是否也含有增殖细胞、这些细胞的身份及其分化为成熟神经元的能力仍不清楚。在这里,我们发现胶质细胞和壁细胞亚型表现出 NSC 特征,表达内源性有丝分裂标记物 Ki67,并在成年大鼠的 OVLT 和 SFO 中结合外源性有丝分裂标记物 BrdU。在 SFO 中增殖的神经胶质细胞包括 NG2 神经胶质细胞,而在 OVLT 中,NG2 神经胶质细胞和澹细胞似乎都构成了 NSC 库。此外,与毛细血管相关的壁细胞--周细胞,也是成年大鼠 OVLT 和 SFO 中构成增殖的细胞池的组成部分。除了这些神经胶质细胞和壁细胞外,一部分含有增殖标记物 Ki67 和 BrdU 的 NSCs 也表达有丝分裂后早期神经元标记物双皮质素,这表明这些 CVO 由新生神经元组成。值得注意的是,这些神经元可以分化并表达成熟神经元标记 NeuN。这些发现确立了感觉 CVO OVLT 和 SFO 是额外的神经源龛,在这些龛中,新神经元和胶质细胞的生成在成人大脑中持续存在。
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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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