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Adult Neurogenesis of the Median Eminence Contributes to Structural Reconstruction and Recovery of Body Fluid Metabolism in Hypothalamic Self-Repair

ABSTRACT: Purpose: To investigate the underlying regulatory mechanism of neurobiology induced by hypothalamic injury from basic gene expression profile, we extracted RNA from hypothalamic median eminence (ME) RNA sequencing (RNA-seq), at day 1 after control and PEL surgery. Results: We identified 811 differentially expressed genes (DEGs, defined as adjust p value < 0.05) between PEL_1d (day 1 after PEL) and control group. Conclusions:We revealed that RNA-seq based transcriptome characterization would expedite genetic network analyses of hypothalamic ME and permit the dissection of complex biologic functions during the process of central diabetes insipidus after PEL surgery.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE187602 | GEO | 2024/01/01

REPOSITORIES: GEO

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Transcriptomic Analysis Reveals that Atf3/c-Jun/Lgals3 axis is associated with Central Diabetes Insipidus after Hypothalamic Injury

Project description:Purpose: To investigate the underlying regulatory mechanism of neurodegeneration induced by hypothalamic injury from basic gene expression profile, we extracted RNA from hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) RNA sequencing (RNA-seq), at day 1 and day 7 after PEL surgery. Results: We identified 1711 differentially expressed genes (DEGs, defined as adjust p value < 0.05) between PEL_1d (day 1 after PEL) and control group, 185 DEGs between PEL_7d (day 7 after PEL) and control group, respectively. Conclusions: We revealed that RNA-seq based transcriptome characterization would expedite genetic network analyses of hypothalamic SON, PVN and permit the dissection of complex biologic functions during the process of central diabetes insipidus after PEL surgery.

2024-01-01 | GSE167904 | GEO

Single-cell Transcriptomic Profiling of the Hypothalamic Median Eminence during Aging

Project description:Aging is a slow and progressive natural process that compromises the normal functions of cells, tissues, organs and systems. The aging of the hypothalamic median eminence (ME), a structural gate linking neural and endocrine systems, may impair hormone release, energy homeostasis and central sensing of circulating molecules, leading to systemic and reproductive aging. However, the molecular and cellular features of ME aging remain largely unknown. Here we describe the transcriptional landscape of young and middle-aged mouse ME at single-cell resolution, revealing the common and cell-type-specific transcriptional changes with age. The transcriptional changes in cell-intrinsic programs, cell-cell crosstalk and cell-extrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular, signaling and molecular levels. Importantly, our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome. Together, our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process, which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.

2022-02-03 | GSE179442 | GEO

Single-cell Transcriptomic Profiling of the Hypothalamic Median Eminence during Aging

Project description:Single-cell Transcriptomic Profiling of the Hypothalamic Median Eminence during Aging

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Effect of pituitary stalk electrical lesion (PEL) and growth hormone (GH) treatment on hypothalamic and hippocampal gene expression

Project description:To investigate the effects of PEL and GH treatment on hypothalamic and hippocampal gene expression, we established a PEL model and administered GH treatment, and then we performed gene expression profiling using data obtained from RNA-seq of 12 different tissues at two time points

2024-05-29 | GSE229838 | GEO

MCH Neurons Regulate Permeability of the Median Eminence Barrier.

Project description:Melanin-concentrating hormone (MCH)-expressing neurons are key regulators of energy and glucose homeostasis. Here, we demonstrate that they provide dense projections to the median eminence (ME) in close proximity to tanycytes and fenestrated vessels. Chemogenetic activation of MCH neurons as well as optogenetic stimulation of their projections in the ME enhance permeability of the ME by increasing fenestrated vascular loops and enhance leptin action in the arcuate nucleus of the hypothalamus (ARC). Unbiased phosphoRiboTrap-based assessment of cell activation upon chemogenetic MCH neuron activation reveals MCH-neuron-dependent regulation of endothelial cells. MCH neurons express the vascular endothelial growth factor A (VEGFA), and blocking VEGF-R signaling attenuates the leptin-sensitizing effect of MCH neuron activation. Our experiments reveal that MCH neurons directly regulate permeability of the ME barrier, linking the activity of energy state and sleep regulatory neurons to the regulation of hormone accessibility to the ARC.

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Median eminence myelin continuously turns over in adult mice.

Project description:ObjectiveOligodendrocyte progenitor cell differentiation is regulated by nutritional signals in the adult median eminence (ME), but the consequences on local myelination are unknown. The aim of this study was to characterize myelin plasticity in the ME of adult mice in health or in response to chronic nutritional challenge and determine its relevance to the regulation of energy balance.MethodsWe assessed new oligodendrocyte (OL) and myelin generation and stability in the ME of healthy adult male mice using bromodeoxyuridine labelling and genetic fate mapping tools. We evaluated the contribution of microglia to ME myelin plasticity in PLX5622-treated C57BL/6J mice and in Pdgfra-Cre/ERT2;R26R-eYFP;Myrffl/fl mice, where adult oligodendrogenesis is blunted. Next, we investigated how high-fat feeding or caloric restriction impact ME OL lineage progression and myelination. Finally, we characterized the functional relevance of adult oligodendrogenesis on energy balance regulation.ResultsWe show that myelinating OLs are continuously and rapidly generated in the adult ME. Paradoxically, OL number and myelin amounts remain remarkably stable in the adult ME. In fact, the high rate of new OL and myelin generation in the ME is offset by continuous turnover of both. We show that microglia are required for continuous OL and myelin production, and that ME myelin plasticity regulates the recruitment of local immune cells. Finally, we provide evidence that ME myelination is regulated by the body's energetic status and demonstrate that ME OL and myelin plasticity are required for the regulation of energy balance and hypothalamic leptin sensitivity.ConclusionsThis study identifies a new mechanism modulating leptin sensitivity and the central control of energy balance and uncovers a previously unappreciated form of structural plasticity in the ME.

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Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence.

Project description:Reproductive competence in mammals depends on the projection of gonadotropin-releasing hormone (GnRH) neurons to the hypothalamic median eminence (ME) and the timely release of GnRH into the hypothalamic-pituitary-gonadal axis. In adult rodents, GnRH neurons and the specialized glial cells named tanycytes periodically undergo cytoskeletal plasticity. However, the mechanisms that regulate this plasticity are still largely unknown. We demonstrate that Semaphorin7A, expressed by tanycytes, plays a dual role, inducing the retraction of GnRH terminals and promoting their ensheathment by tanycytic end feet via the receptors PlexinC1 and Itgb1, respectively. Moreover, Semaphorin7A expression is regulated during the oestrous cycle by the fluctuating levels of gonadal steroids. Genetic invalidation of Semaphorin7A receptors in mice induces neuronal and glial rearrangements in the ME and abolishes normal oestrous cyclicity and fertility. These results show a role for Semaphorin7A signalling in mediating periodic neuroglial remodelling in the adult ME during the ovarian cycle.

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A molecular census of arcuate hypothalamus and median eminence cell types.

Project description:The hypothalamic arcuate-median eminence complex (Arc-ME) controls energy balance, fertility and growth through molecularly distinct cell types, many of which remain unknown. To catalog cell types in an unbiased way, we profiled gene expression in 20,921 individual cells in and around the adult mouse Arc-ME using Drop-seq. We identify 50 transcriptionally distinct Arc-ME cell populations, including a rare tanycyte population at the Arc-ME diffusion barrier, a new leptin-sensing neuron population, multiple agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) subtypes, and an orexigenic somatostatin neuron population. We extended Drop-seq to detect dynamic expression changes across relevant physiological perturbations, revealing cell type-specific responses to energy status, including distinct responses in AgRP and POMC neuron subtypes. Finally, integrating our data with human genome-wide association study data implicates two previously unknown neuron populations in the genetic control of obesity. This resource will accelerate biological discovery by providing insights into molecular and cell type diversity from which function can be inferred.

| S-EPMC5323293 | biostudies-literature

Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche.

Project description: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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The Median Eminence, A New Oligodendrogenic Niche in the Adult Mouse Brain.

Project description:The subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus are known as neurogenic niches. We show that the median eminence (ME) of the hypothalamus comprises BrdU+ newly proliferating cells co-expressing NG2 (oligodendrocyte progenitors) and RIP (pre-myelinating oligodendrocytes), suggesting their differentiation toward mature oligodendrocytes (OLs). ME cells can generate neurospheres (NS) in vitro, which differentiate mostly to OLs compared with SVZ-NS that typically generate neurons. Interestingly, this population of oligodendrocyte progenitors is increased in the ME from experimental autoimmune encephalomyelitis (EAE)-affected mice. Notably, the thrombospondin 1 (TSP1) expressed by astrocytes, acts as negative regulator of oligodendrogenesis in vitro and is downregulated in the ME of EAE mice. Importantly, transplanted ME-NS preferentially differentiate to MBP+ OLs compared with SVZ-NS in Shiverer mice. Hence, discovering the ME as a new site for myelin-producing cells has a great importance for advising future therapy for demyelinating diseases and spinal cord injury.

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