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: 14.98). 03/2012; 15(5):700-2. DOI: 10.1038/nn.3079
Source: PubMed

ABSTRACT 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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Available from: Seth Blackshaw, Aug 21, 2015
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    • "We observed no long-term differences in body weight gained between sham and irradiated animals fed normal chow in either our male (sham treatment: n=8; irradiation treatment: n=12) or female (sham treatment: n=12; irradiation treatment: n=12) cohorts (Figure 3C). In contrast, HFD-fed female mice showed a significant reduction in weight gain following irradiation relative to sham controls, as previously reported (Lee et al., 2012). At 9 weeks post-treatment, irradiated female mice receiving HFD (n=10) had 32±4% increase in weight gain relative to sham controls (n=9), which showed a 52±6% increase in weight gain (student t-test: p=0.028 Figure 3C). "
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    ABSTRACT: The hypothalamus is the central regulator of a broad range of homeostatic and instinctive physiological processes, such as the sleep-wake cycle, food intake, and sexually dimorphic behaviors. These behaviors can be modified by various environmental and physiological cues, although the molecular and cellular mechanisms that mediate these effects remain poorly understood. Recently, it has become clear that both the juvenile and adult hypothalamus exhibit ongoing neurogenesis, which serve to modify homeostatic neural circuitry. In this report, we share new findings on the contributions of sex-specific and dietary factors to regulating neurogenesis in the hypothalamic mediobasal hypothalamus, a recently identified neurogenic niche. We report that high fat diet (HFD) selectively activates neurogenesis in the median eminence of young adult female but not male mice, and that focal irradiation of HFD-fed mice likewise reduces weight gain in females but not males. These findings suggest that the physiological effects of high fat diet may be mediated by the stimulation of neurogenesis in the hypothalamic median eminence in a sexually dimorphic manner. We discuss these results in the context of recent advances in understanding the cellular and molecular mechanisms that regulate neurogenesis in postnatal and adult hypothalamus.
    Frontiers in Neuroscience 06/2014; DOI:10.3389/fnins.2014.00157 · 3.70 Impact Factor
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    • " find evidence that dividing cells adopted a neuronal phenotype in this region ( Hazlerigg et al . , 2013 ) . Interesting , from other model systems there is some evidence that blockade of cell division in the mediobasal hypothalamus using anti - mitotic compounds or irradiation ameliorated leptin - ( Kokoeva et al . , 2005 ) and high fat diet - ( Lee et al . , 2012 ) induced changes in metabolism , suggesting a causal role for cell division in hypothalamic function . It remains to be determined whether thyroid hormone is the critical regulator of seasonal plasticity in the adult hypothalamus . Because thyroid hormone is the critical regulator for neurogenesis in the subventricular zone of mice ( L"
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    ABSTRACT: This article is part of a Special Issue “Energy Balance”. Seasonal cycles of adiposity and body weight reflecting changes in both food intake and energy expenditure are the norm in mammals that have evolved in temperate and polar habitats. Innate circannual rhythmicity and direct responses to the annual change in photoperiod combine to ensure that behavior and energy metabolism are regulated in anticipation of altered energetic demands such as the energetically costly processes of hibernation, migration, and lactation. In the last decade, major progress has been made into identifying the central mechanisms that underlie these profound long-term changes in behavior and physiology. Surprisingly they are distinct from the peptidergic and aminergic systems in the hypothalamus that have been identified in studies of the laboratory mouse and rat and implicated in timing meal intervals and in short-term responses to caloric restriction. Comparative studies across rodents, ungulates and birds reveal that tanycytes embedded in the ependymal layer of the third ventricle play a critical role in seasonal changes because they regulate the local availability of thyroid hormone. Understanding how this altered hormonal environment might regulate neurogenesis and plasticity in the hypothalamus should provide new insight into development of strategies to manage appetite and body weight.
    Hormones and Behavior 06/2014; 66(1). DOI:10.1016/j.yhbeh.2014.03.009 · 4.51 Impact Factor
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    • "Despite not having classical features of a neurogenic niche, median eminence tanycytes may also generate new-born neurons (Kokoeva et al., 2005; Lee et al., 2012). After a first study supporting the idea that hypothalamic neurogenesis in adult mice has a role in the control of energy-balance, including the capacity of regulating leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) (Kokoeva et al., 2005), another recent work showed that median eminence tanycytes have a role in regulating the weight and metabolic activity of adult mice (Lee et al., 2012). "
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    ABSTRACT: Adult neurogenesis is a lifelong process that occurs in two main neurogenic niches of the brain, namely in the subventricular zone (SVZ) of the lateral ventricles and in the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus. In the 1960s, studies on adult neurogenesis have been hampered by the lack of established phenotypic markers. The precise tracing of neural stem/progenitor cells (NPCs) was therefore, not properly feasible. After the (partial) identification of those markers, it was the lack of specific tools that hindered a proper experimental elimination and tracing of those cells to demonstrate their terminal fate and commitment. Nowadays, irradiation, cytotoxic drugs as well as genetic tracing/ablation procedures have moved the field forward and increased our understanding of neurogenesis processes in both physiological and pathological conditions. Newly formed NPC progeny from the SVZ can replace granule cells in the olfactory bulbs of rodents, thus contributing to orchestrate sophisticated odor behavior. SGZ-derived new granule cells, instead, integrate within the DG where they play an essential role in memory functions. Furthermore, converging evidence claim that endogenous NPCs not only exert neurogenic functions, but might also have non-neurogenic homeostatic functions by the release of different types of neuroprotective molecules. Remarkably, these non-neurogenic homeostatic functions seem to be necessary, both in healthy and diseased conditions, for example for preventing or limiting tissue damage. In this review, we will discuss the neurogenic and the non-neurogenic functions of adult NPCs both in physiological and pathological conditions.
    Frontiers in Neuroscience 04/2014; 8:92. DOI:10.3389/fnins.2014.00092 · 3.70 Impact Factor
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