Tanycytes of the Hypothalamic Median Eminence Form a Diet-Responsive Neurogenic Niche

Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nature Neuroscience (Impact Factor: 16.1). 03/2012; 15(5):700-2. DOI: 10.1038/nn.3079
Source: PubMed


Adult hypothalamic neurogenesis has recently been reported, but the cell of origin and the function of these newborn neurons are unknown. Using genetic fate mapping, we found that median eminence tanycytes generate newborn neurons. Blocking this neurogenesis altered the weight and metabolic activity of adult mice. These findings reveal a previously unreported neurogenic niche in the mammalian hypothalamus with important implications for metabolism.

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    • "Moreover, because of the significant up-amplification of NSCs after stroke, proliferating subependymal NSCs in 3V (Fig. 2B–D) and 4V (Fig. 2G) niches, predominantly on the side of the injury, were additionally detected for the first time (Lin et al., 2015). Also as widely reported previously (Barnabé- Heider et al., 2010; Carlén et al., 2009; Ekdahl et al., 2009; Lindvall and Kokaia, 2008; Robins et al., 2013), enhanced proliferation of ependymal tanycytes lining the mid-level 3V was also observed ipsilaterally after stroke (Fig. 2D, E) or other inductive stimuli (Lee et al., 2012a, 2012b; Migaud et al., 2010; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). It is unlikely that stem cells in these novel ventricular locations have migrated there from more classic niche sites since virally-labeled SVZ NSCs do not appear in the 3V or 4V niches after MCAO (Lin et al., 2015). "
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    ABSTRACT: Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. Copyright © 2015. Published by Elsevier B.V.
    Brain research 04/2015; 219. DOI:10.1016/j.brainres.2015.04.029 · 2.84 Impact Factor
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    • "Thus, our current results are the first to demonstrate that FLX targets hypothalamic tanycytes. Several prior studies have suggested that ependymal cells (Johansson et al., 1999) or tanycytes (Lee et al., 2012) represent the resident NPC populations in the adult mammalian hypothalamus. Whether FLX leads to changes in tanycyte function has remained unknown, but the increased number of nestin/Tomato+ cells following chronic FLX "
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    ABSTRACT: Chronic treatment with antidepressants has been shown to enhance neurogenesis in the adult mammalian brain. Although this effect was initially reported to be restricted to the hippocampus, recent work has suggested that fluoxetine, a selective serotonin reuptake inhibitor, also promotes neurogenesis in the cortex. However, whether antidepressants target neural progenitor cells in other brain regions has not been examined. Here, we used BrdU labeling and immunohistochemistry with a transgenic mouse line in which nestin+ neural progenitor cells can be inducibly labeled with the fluorescent protein, Tomato, following tamoxifen administration. We investigated the effects of chronic fluoxetine on cell proliferation and nestin+ progenitor cells in periventricular areas in the medial hypothalamus and medial habenula, two brain areas involved in stress and anxiety responses. Our data provide the first in vivo evidence that fluoxetine promotes cell proliferation and neurogenesis and increases the mRNA levels of BDNF in the hypothalamus and habenula. By identifying novel cellular targets of fluoxetine, our results may provide new insight into the mechanisms underlying antidepressant responses. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    The International Journal of Neuropsychopharmacology 10/2014; 18(4). DOI:10.1093/ijnp/pyu029 · 4.01 Impact Factor
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    • "Accumulated evidence suggests that there are multiple neurogenic niches in the brain apart from the hippocampal dentate gyrus sub granular zone (SGZ) and the cerebral sub ventricular zone (SVZ). These include the hypothalamus (Lee et al., 2012), cerebellum (Keller et al., 2004; Ponti et al., 2005, 2006, 2008, 2010; Bonfanti and Ponti, 2008; Hajihosseini et al., 2008), striatum (Tattersfield et al., 2004; Ninomiya et al., 2006; Luzzati et al., 2007; Snyder et al., 2010; Danilov et al., 2012; Delavaran et al., 2013; Ernst et al., 2014; Kempermann, 2014), and SN (Bayer et al., 1995; Zhao et al., 2003; Chen et al., 2005; Van Kampen and Robertson, 2005; Yoshimi et al., 2005; Arias-Carrión et al., 2006, 2009; Freundlieb et al., 2006; Shan et al., 2006; Steiner et al., 2006; Esposito et al., 2007; Mandel et al., 2007; Di Giovanni et al., 2009; Ries et al., 2009; Park et al., 2012; Sun et al., 2012a,b; Worlitzer et al., 2013). Therefore, APα may promote the generation of new cells locally in SN. "
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    ABSTRACT: Reinstalling the neurobiological circuits to effectively change the debilitating course of neurodegenerative diseases is of utmost importance. This reinstallation requires generation of new cells which are able to differentiate into specific types of neurons and modification of the local environment suitable for integration of these new neurons into the neuronal circuits. Allopregnanolone (APα) seems to be involved in both of these processes, and therefore, is a potential neurotrophic agent. Loss of dopamine neurons in the substantia nigra (SN) is one of the main pathological features of Parkinson's and also in, at least, a subset of Alzheimer's patients. Therefore, reinstallation of the dopamine neurons in nigrostriatal tract is of unique importance for these neurodegenerative diseases. However, for the neurogenic status and the roles of allopregnanolone in the nigrostriatal tract, the evidence is accumulating and debating. This review summarizes recent studies regarding the neurogenic status in the nigrostriatal tract. Furthermore, special attention is placed on evidence suggesting that reductions in allopregnenalone levels are one of the major pathological features in PD and AD. This evidence has also been confirmed in brains of mice that were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or those bearing neurodegenerative mutations. Lastly, we highlight studies showing that allopregnanalone can augment the number of total cells and dopaminergic neurons via peripheral exogenous administration.
    Frontiers in Cellular Neuroscience 08/2014; 8:224. DOI:10.3389/fncel.2014.00224 · 4.29 Impact Factor
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