Novel Neuronal Phenotypes from Neural Progenitor Cells

Abstract

We report the first isolation of progenitor cells from the hypothalamus, a derivative of the embryonic basal plate that does not exhibit neurogenesis postnatally. Neurons derived from hypothalamic progenitor cells were compared with those derived from progenitor cultures of hippocampus, an embryonic alar plate derivative that continues to support neurogenesis in vivo into adulthood. Aside from their different embryonic origins and their different neurogenic potential in vivo, these brain regions were chosen because they are populated with cells of three different categories: Category I cells are generated in both hippocampus and hypothalamus, Category II cells are generated in the hypothalamus but are absent from the hippocampus, and Category III is a cell type generated in the olfactory placode that migrates into the hypothalamus during development. Stem-like cells isolated from other brain regions, with the ability to generate neurons and glia, produce neurons of several phenotypes including gabaergic, dopaminergic, and cholinergic lineages. In the present study, we extended our observations into neuroendocrine phenotypes. The cultured neural precursors from 7-week-old rat hypothalamus readily generated neuropeptide-expressing neurons. Hippocampal and hypothalamic progenitor cultures converged to indistinguishable populations and produced neurons of all three categories, confirming that even short-term culture confers or selects for immature progenitors with enough plasticity to elaborate neuronal phenotypes usually inhibited in vivo by the local microenvironment. The range of phenotypes generated from neuronal precursors in vitro now includes the peptides found in the neuroendocrine system: corticotropin-releasing hormone, growth hormone-releasing hormone, gonadotropin-releasing hormone, oxytocin, somatostatin, thyrotropin-releasing hormone, and vasopressin.

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

“…5e,f). Both early-and late-passage neurospheres differentiated after growth factor reduction, as assessed by the presence of RIP þ ive oligodendrocytes 34 , GFAP þ cells with astrocytic morphology 35 , TUJ1 þ ve immature neurons 36,37 and growth hormone releasing hormone (GHRH) þ ive hypothalamic neurons 32 (Fig. 5g).…”

Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain

“…Indeed, a study in 1996 and additional ones later on reported that cells surrounding the third ventricle could generate neurospheres (Weiss et al 1996;Xu et al 2005;Li et al 2012;Robins et al 2013) and monolayer cell culture generating neurons and glia (Markakis et al 2004). Based on 24-h post-BrdU experiments, proliferative cells have been identified in both the parenchyma and along the third ventricle (for a review, see Migaud et al 2010).…”

Efficient non-viral transfection of adult neural stem/progenitor cells, without affecting viability, proliferation or differentiation

“…Moreover, a recent study has shown that the TRH peptide is present in adult hippocampal NSPCs 122 , suggesting that TRH may affect these cells in a paracrine or autocrine manner.…”

“…Interestingly, a recent study has shown that the TRH peptide is present in adult hippocampal stem/progenitor cells 122 . This suggests that TRH may act as an autocrine or paracrine modulator of NSPC proliferation.…”