The existence of a specialized class of ependymolyal cells in the hypothalamus has been known since the early 20th century. Indeed, starting around 1909, both Santiago Ramón y Cajal and Giuseppe Sterzi independently described elongated cells resembling radial glia in the infundibular or tuberal region of vertebrates, including mammals, with cell bodies lining the ventricular wall and long processes extending out extend to the pial surface . Ramon y Cajal, 1909; Stezi, 1909). Because of this structure, named by Ernst Horstmann in 1954 after the Greek term for “stretched cells” (Horstmann, 1954), tanycytes are not just passive members of the neuroglial and neurovascular components of the hypothalamus, but dynamic, responsive cells, often with a permissive or regulatory function . Indeed, a growing body of studies underscores the versatility of these cells and their critical involvement in a wide range of biological processes, from energy homeostasis and metabolism to the control of reproduction and other hypothalamic-pituitary axes and more. Although most of the knowledge about tanycytes comes from animal models, neuroanatomical studies of the hypothalamus using postmortem tissue (Baroncini et al., 2007; Sidibe et al., 2010; Koopman et al., 2017; Pellegrino et al., 2018) as well as some imaging Studies of the brain in living patients (Baroncini et al., 2010; Denis et al., 2020) support the extrapolation of these physiological and pathological features to humans (reviewed in Prevot et al., 2018).
The center of the diverse function of tanycytes is their special location. In fact, they form a bridge between the cerebrospinal fluid (CSF) and the perivascular space bordering the middle hypothalamus (ME), one of the seven circumventricular organs (CVO) bordering the arcuate nucleus of the hypothalamus (ARH) in humans as the nucleus infundibularis, where they are in contact with the peripheral circulation via the fenestrated endothelium of the hypothalamic-pituitary portal capillaries (Fig. 16.1). This privileged position at the blood-brain and blood-CSF interfaces allows tanycytes to replace the traditional blood-brain barrier (BBB) or to modulate its function. Their morphological plasticity in response to the physiological and hormonal environment allows them to relay metabolic signals and circulating hormones in the brain and modulate the brain's secretion of neuroendocrine factors into the circulation (reviewed in Prevot et al., 2018; Banks, 2019; García-Caceres et al., 2019). In recent years, several new roles have been added to the tanycytes' repertoire, often at the interface between energy metabolism and reproduction: (i) They appear to be actively involved not only in the transport but also in the sensing of metabolic signals and the transmission of this information to the neurons; (ii) possess the properties of neural stem cells (NSCs), adding adult hypothalamic neurogenesis to the mechanisms by which the brain maintains metabolic balance or reproductive capacity; and (iii) they can mediate inflammatory pathogenesis, including aging, in the brain in a variety of ways.
This chapter briefly summarizes the current knowledge of these fascinating cells and the cellular and molecular mechanisms underlying their potential role as a giant control panel that enables efficient, appropriate, and adaptive exchange of information between the brain and the periphery, and between the neural circuits that regulate various physiological functions.
Origin and classification of tannycytes
Like Bergmann's cerebellar glia, tanycytes are residual radial glial cells in the mammalian brain whose typical structure and many of their features persist throughout life (Goodman and Hajihosseini, 2015; Rizzoti and Lovell-Badge, 2017). The traditional view classifies tanycytes into four subtypes: α1, α2, β1, and β2 based on their dorsoventral position along the ventricular wall, the trajectory of their processes, and their histological features (Akmayev et al.
As mentioned above, the morphology and location of tanycytes are closely related to their various roles. Consistent with their ontogeny, tanycytes have a radial morphology with a cell body lining the wall of the third ventricle and long, sometimes branching, processes that cross the hypothalamic parenchyma to terminate in the traditional BBB capillaries or in the perivascular space of fenestrated capillaries end up. of the hypothalamic-pituitary portal system (Fig. 16.1F and G).
Functional specialization of tannycytes
Tanyocytes are at the crossroads of several physiological processes. As knowledge of their biology advances, overlapping molecules and signaling pathways emerge, both between the major physiological processes they are involved in (reproduction and energy homeostasis) and linking newly discovered functions, such as B. their role as stem / progenitor cells or their properties. flammable. . It is therefore necessary to consider the functions described below as parts of a whole and not as discrete functions.
At the interface between the peripheral bloodstream, the hypothalamic parenchyma, and the cerebrospinal fluid in a part of the brain extremely rich in hormone-producing and hormone-responsive elements, tanycytes are uniquely located to dynamically mediate and interconnect these various processes. . . These processes are all the more important since the hypothalamus itself is the coordination center for numerous homeostatic processes without which life cannot exist. While the subtypes of
expression of gratitude
We thank Dr. Rasika for editing the manuscript. The authors are supported by the European Research Council's Synergy Program under Grant Agreement No. 810331.
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Pharmacotherapy of obesity: effects of incretins on the central nervous system
2023, Trends in the Pharmacological Sciences
The prevalence of obesity is increasing, creating an urgent need for effective therapies. Recent clinical studies show that tirzepatide, a dual agonist of the incretin hormone receptors glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), causes greater weight loss than the selective receptor for GLP-1 ( GLP -1). 1R) agonists. Incretin receptors in the central nervous system (CNS) may contribute to these effects. However, it is not clearly understood how each receptor regulates body weight within the CNS. It remains unclear how GIP receptor (GIPR) signaling contributes to the effects of tirzepatide, as both stimulation and inhibition of CNS GIPRs result in weight loss in preclinical models. We summarize the current knowledge on the pharmacology of the CNS incretin receptor to provide insight into potential mechanisms of action of GIPR/GLP-1R dual agonists using the example of tirzepatide. In addition, we discuss recent developments in incretin-based dual and triagonistic agonism for weight loss in obese people.(Video) Blood Brain Barrier (part 2): Circumventricular organs, hypothalamus hypophyseal system USMLE minute
Tanycytes control hypothalamic uptake of liraglutide and its anti-obesity effects
2022, cellular metabolism
Liraglutide, an antidiabetic and glucagon-like peptide receptor (GLP1R) agonist, was recently approved for the treatment of obesity in people with or without type 2 diabetes. Despite its broad metabolic benefits, the mechanism and site of action of liraglutide remain unclear . Here we show that liraglutide is transported to target cells in the mouse hypothalamus by specialized ependymolial cells called tanycytes, bypassing the blood-brain barrier. Selectively turning off the GLP1R in tanycytes or inhibiting tanycytic transcytosis via botulinum neurotoxin expression not only impedes liraglutide transport into the brain and its activation of hypothalamic target neurons, but also blocks its anti-obesity effect on food intake, body weight and fat mass and fat acid oxidation. Taken together, these remarkable data indicate that liraglutide-induced activation of hypothalamic neurons and their subsequent metabolic effects are mediated through their tannycyte transport to the mediobasal hypothalamus, reinforcing the notion of tanycytes as key regulators of metabolic homeostasis.
Melatonin in ventricular and subarachnoid cerebrospinal fluid: its role in the neural glymphatic network and biological importance for neurocognitive health
2022, Biochemical and Biophysical Research Communications
The central nervous system (CNS) is equipped with a specialized network of cerebrospinal fluid (CSF) and lymph that removes toxic molecules and metabolic byproducts from the neural parenchyma; collectively this has been called the glymphatic system. It allows CSF located in the subarachnoid space around the CNS to penetrate deep into the brain and spinal cord through the perivascular and perivenous Virchow-Robin spaces. CSF in the periarterial spaces is carried through the astrocytic feet lining these spaces by means of AQ4 channels; In the interstitium, fluid moves through the parenchyma by convection to eventually reach the perivenous spaces. In passing through the nerve tissue, the interstitial fluid expels metabolic byproducts and extracellular toxins and debris into the cerebrospinal fluid of the perivenous spaces. The fluid then moves to the surface of the CNS where the contaminants are absorbed into the true lymphatics of the dura mater, from where they are diverted from the skullcap to the cervical lymph nodes. Pineal melatonin, which is released directly into the cerebrospinal fluid, causes the concentration of this molecule in the cerebrospinal fluid of the third ventricle to be much higher than in the blood. After ventricular melatonin enters the subarachnoid and Virchow-Robin spaces, it is transported to nerve tissue where it acts as a powerful antioxidant and anti-inflammatory agent. Experimental evidence suggests that pathogenic toxins, e.g. B. amyloid-β and others, removed from the brain to protect against neurocognitive degradation. Melatonin levels decline significantly during aging, which coincides with the development of various neurodegenerative diseases and the accumulation of associated neurotoxins.
Blood Glucose Control: Tanicitos march to the beat of the suprachiasmatic drummer
2022, Current Biology
The suprachiasmatic nucleus (SCN) synchronizes physiology with the individual's environment to optimize bodily functions. A new study shows that tannycytes follow the rhythm established by the SCN to effect circadian changes in both blood glucose entry and blood glucose to the brain.(Video) Blood Brain Barrier: Circumventricular organ (part 4), OVLT, Renin, Angiotensin USMLE in 3 minute
Astrocytes in neural circuits that control appetite and food intake.
2022, Current opinion in endocrine and metabolic research
The regulation of eating behavior is a complex process controlled by neural circuits in the brain. In addition to neurons, genetic and pharmacological studies in animal models indicate that glial cells, including astrocytes, are important components of these neuronal circuits. This review provides the latest evidence (published since 2019) from different brain regions on the contribution of astrocytes to the regulation of neural circuits that control appetite and food intake, including eating when hungry to meet energy needs (homeostatic nutrition) and hedonic eating for pleasure without energy requirements (non-homeostatic nutrition). The brain regions studied include the hypothalamus, the dorsal vagal complex of the rhombencephalon, and the mesolimbic and corticostriatal systems. The emerging problem of a potential astrocyte energetics model of neural circuit regulation in the context of feeding behavior is assessed.
Featured Articles (6)
The role of the dorsomedial and ventromedial hypothalamus in behavioral and resting autonomic impulse regulation
Handbook of Clinical Neurology, Vol. 180, 2021, pp. 187-200
Almost a century ago it was reported that stimulation of the hypothalamus could lead to profound changes in behavioral status along with altered autonomic function. Since these initial observations, subsequent animal studies have shown that two hypothalamic regions, the dorsomedial and ventromedial hypothalamic nuclei, are central to numerous behaviors, including those responsive to psychological stressors. These behaviors are combined with changes in autonomic functions such as altered blood pressure, heart rate, sympathetic nerve activity, restoration of the baroreflex, and changes in pituitary function. There is also growing evidence that these two hypothalamic regions play a central role in thermogenesis, and it has been suggested that they may also be responsible for obesity-related hypertension. The aim of this chapter is to review the anatomy, projection pattern and function of the dorsomedial and ventromedial hypothalamus with a particular emphasis on their role in autonomic regulation. While most of what is known about these two hypothalamic regions comes from experiments in laboratory animals, more recent human studies are also examined. Finally, we will describe recent human brain imaging studies that provide evidence for the role of these hypothalamic regions in establishing resting-state sympathetic drive and their potential role in conditions such as hypertension.
The human hypothalamic kisspeptin system: functional neuroanatomy and clinical perspectives
Handbook of Clinical Neurology, Vol. 180, 2021, pp. 275-296
In mammals, kisspeptin neurons are key components of hypothalamic neuronal networks that regulate the onset of puberty, are responsible for pulsatile secretion of gonadotropin-releasing hormone (GnRH), and mediate positive and negative feedback signals from estrogen to GnRH neurons. Because the large kisspeptin cell clusters of the preoptic area/rostral hypothalamus/arcuate (or infundibular) nucleus are anatomically and functionally directly connected to the hypophysiotropic GnRH system, they are ideally positioned to serve as key nodes that control various types of environmental conditions integrate , endocrine and metabolic signals that can affect fertility.
This chapter provides an overview of the current state of knowledge on the anatomy, functions, and plasticity of kisspeptin systems in the brain, based on the extensive available literature from various laboratory and pet species. Then the species-specific properties of human kisspeptin hypothalamic neurons are described, covering their topography, morphology, unique neuropeptide content, plasticity, and connectivity to hypophysiotropic GnRH neurons. Some emerging roles of central kisspeptin signaling in behavior and finally clinical perspectives are discussed.
Electrical stimulation of the fornix to treat brain disorders
Handbook of Clinical Neurology, Vol. 180, 2021, pp. 447-454
Deep brain stimulation (DBS) has been shown to be safe and effective in both hypokinetic and hyperkinetic movement disorders originating in the basal ganglia, while its application to other neural pathways such as the cerebral circulation is being explored. In particular, the fornix has attracted interest as a potential DBS target to reduce rates of cognitive decline, improve memory, aid in visuo-spatial memory, and improve verbal recall. While the exact mechanisms of action of Fornix DBS are not fully understood, studies have found increased release of acetylcholine in the hippocampus, synaptic plasticity, and decreased inflammatory responses in the cortex and hippocampus. However, it is still premature to conclude that DBS with Fornix can be used in the treatment of cognitive disorders, and the field needs robust, preclinically tested, disease-specific post-hypotheses.
The subfornic organ and the organum vasculosum of the lamina terminalis: crucial roles in cardiovascular regulation and fluid balance control.
Handbook of Clinical Neurology, Vol. 180, 2021, pp. 203-215
In this chapter, we review the extensive literature describing the role of the subfornic organ (SFO), the organum vasculosum of the terminalis (OVLT), and the median preoptic nucleus (MnPO), which encompasses the lamina terminalis, in cardiovascular regulation and control describes . . . the fluid balance. We present this information in the context of historical and technological developments, which may well overlap. We describe the intrinsic anatomy and connectivity, and then discuss early work describing how circulating angiotensin II in the SFO acts to stimulate alcohol consumption and increase blood pressure. Subsequently, extensive studies using direct delivery and lesion approaches are discussed to highlight the role of all regions of the lamina terminalis. At the cellular level, we describe c-Fos and electrophysiological work that has highlighted an extensive panel of circulating hormones that appear to affect the activity of specific neurons in SFO, OVLT, and MnPO. We highlight optogenetic studies that have begun to unravel the complexity of the circuitry underlying physiological outcomes, particularly those related to the various beverage components. Finally, we describe the somewhat limited human literature that supports the conclusions that these structures play similar and potentially important roles in human physiology.
Handbook of Clinical Neurology, Volume 180, 2021, pp. ix-xi
Handbook of Clinical Neurology, Volume 180, 2021, p. viii
Copyright © 2021 Elsevier B.V. All rights reserved.
What is the role of tanycytes? ›
Tanycytes, glial-like cells that line the third ventricle, are emerging as components of the hypothalamic networks that control body weight and energy balance. They contact the cerebrospinal fluid (CSF) and send processes that come into close contact with neurons in the arcuate and ventromedial hypothalamic nuclei.What cell is responsible for the blood-brain barrier? ›
The blood-brain barrier (BBB) is a specialized structure of the central nervous system (CNS) that restricts immune cell migration and soluble molecule diffusion from the systemic compartment into the CNS. Astrocytes and microglia are resident cells of the CNS that contribute to the formation of the BBB.Where are tanycytes? ›
Tanycytes are polarized cells, with cell bodies located in the wall of the third ventricle and elongated processes extending into the parenchyma and contacting the pial surface of the brain. Due to this peculiar morphology and their stem cell properties, tanycytes can be considered radial glia of the mature brain66.How are tanycytes different from ependymal cells? ›
Tanycytes are special ependymal cells found in the third ventricle of the brain, and on the floor of the fourth ventricle and have processes extending deep into the hypothalamus. It is possible that their function is to transfer chemical signals from the cerebrospinal fluid to the central nervous system.Where is the median eminence located? ›
The median eminence is the structure at the base of the hypothalamus where hypothalamic-releasing and –inhibiting hormones converge onto the portal capillary system that vascularizes the anterior pituitary gland.What is the physiological role of hypothalamic tanycytes in metabolism? ›
Tanycytes are modulators of energy balance. By interacting with both neurons and vessels—locally in the mediobasal hypothalamus and globally through the cerebrospinal fluid—tanycytes modulate both orexigenic and anorexigenic pathways and participate in the regulation of glucose homeostasis and energy balance.What causes blood-brain barrier breakdown? ›
Hypertension, diabetes, and hyperlipidemia are the major factors besides age that cause changes in the blood vessels responsible for the impairments in cerebral blood flow and oxygenation, along with increase in permeability.How do T cells cross the blood-brain barrier? ›
Activated T cells can enter the subarachnoid space by migrating from blood vessels into the stroma of the choroid plexus and then crossing the blood–cerebrospinal fluid (CSF) barrier surrounding the choroid plexus stroma, which comprises epithelial cells joined by tight junctions.Which of the following substances that the blood-brain barrier prevents from entering brain tissue? ›
Answer and Explanation: The best answer is (C): Pharmaceuticals. Nicotine and alcohol can cross the blood-brain barrier.What are the different types of tanycytes? ›
Four subtypes of tanycytes (α1, α2, β1, β2) have been described along the 3V wall. In vivo and in vitro studies suggest that α2 tanycytes (also known as dorsomedial ARH tanycytes) (blue) that face the dorsal part of the ARH have NSC properties, while the other tanycyte populations (green) rather behave as NPCs.
Do tanycytes respond to glucose? ›
Both in vitro and in situ studies demonstrated that tanycytes sense and respond to extracellular glucose via a rapid, glucose-activated signal transduction pathway mediated by lactate and/or ATP.What is the role of astrocytes microglia and tanycytes in brain control of systemic metabolism? ›
Astrocytes, microglia, and tanycytes play active roles in the regulation of hypothalamic feeding circuits. These non-neuronal cells are crucial in determining the functional interactions of specific neuronal subpopulations involved in the control of metabolism.What cell types include Ependymocytes and tanycytes? ›
As non-neuronal cells in the brain and derived from neuroectoderm, they are clearly defined as a subtype of glial cells. They include the ependymocytes, choroid plexus epithelial cells, tanycytes, and within the retina, Müller cells and retinal pigment epithelial cells.
- ependymal cells. move cerebrous spinal fluid around to keep it homogenous.
- astrocytes. form the blood brain barrier.
- microglia. they do phagocytosis to fight infection.
- oligodendrocytes. bind the CNS neurons together and insulate the axons.
- schwann cells. insulate PNS axons.