IGF‐I stimulates neurogenesis in the hypothalamus of adult rats

Abstract

In the brain of adult rats neurogenesis persists in the subventricular zone of the lateral ventricles and in the dentate gyrus of the hippocampus. By contrast, low proliferative activity was observed in the hypothalamus. We report here that, after intracerebroventricular treatment with insulin-like growth factor I (IGF-I), cell proliferation significantly increased in both the periventricular and the parenchymal zones of the whole hypothalamus. Neurons, astrocytes, tanycytes, microglia and endothelial cells of the local vessels were stained with the proliferative marker 5-bromo-2'-deoxyuridine (BrdU) in response to IGF-I. Conversely, we never observed BrdU-positive ciliated cubic ependymal cells. Proliferation was intense in the subventricular area of a distinct zone of the mid third ventricle wall limited dorsally by ciliated cubic ependyma and ventrally by tanycytic ependyma. In this area, we saw a characteristic cluster of proliferating cells. This zone of the ventricular wall displayed three cell layers: ciliated ependyma, subependyma and underlying tanycytes. After IGF-I treatment, proliferating cells were seen in the subependyma and in the layer of tanycytes. In the subependyma, proliferating glial fibrillary acidic protein-positive astrocytes contacted the ventricle by an apical process bearing a single cilium and there were many labyrinthine extensions of the periventricular basement membranes. Both features are typical of neurogenic niches in other brain zones, suggesting that the central overlapping zone of the rat hypothalamic wall could be considered a neurogenic niche in response to IGF-I.

α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors

“…Although recent studies have focused attention on b2-tanycytes as proliferating progenitors 22,23 , earlier studies suggested that a-tanycytes may harbour neural stem/progenitor potential in the adult 6,11 . To examine whether adult a-tanycytes possess neural stem/progenitor functions, we searched for an appropriate genetic means to label them.…”

“…In the adult rat, fate-mapping experiments of the hypothalamic ventricular wall first showed that proliferating ependymal cells, including but not exclusively tanycytes, can give rise to progeny that migrate along tanycyte processes 11 . Additional studies in the adult rat revealed an enhanced proliferation of tanycytes in response to IGF-1 6 . In the mouse, lineage-tracing studies have demonstrated that a subset of b-tanycytes, the b2-tanycytes, can proliferate and are neurogenic, contributing new neurons to hypothalamic nuclei in the postnatal/juvenile period 22 .…”

“…These studies have raised the possibility that the adult hypothalamus contains NSCs in a niche near the third ventricle. However, tanycytes, ependymocytes, subventricular astrocytes and parenchymal glial cells all reside near the third ventricle, and each is a potential adult stem and progenitor cell candidate 2,[5][6][7][8][11][12][13] .…”

“…In addition, in vivo analyses show constitutive proliferation, neurogenesis and astrocyte generation within a third region of the adult brain, the hypothalamus [1][2][3][4][5] . Here, neurogenesis and gliogenesis can be attenuated through the manipulation of secreted trophic factors, de novo neurogenesis, in particular, associated with energy balance 1,2,4,6,7 .…”

Intertwining extracellular nucleotides and their receptors with Ca2+in determining adult neural stem cell survival, proliferation and final fate

“…Birth of new neurons that integrate locally in functional circuits underlying hormone production and release has been observed in the hypothalamus in response to insulin-like growth factor 1 (IGF-1) administration, leading to the identification of a specific 'neurogenic niche' in the walls of the third ventricle [19], which will not be analysed in this paper. As mentioned, precursors in neurogenic areas derive from embryonic radial glial cells, whose proliferation and differentiation are tightly controlled by intercellular calcium waves.…”