Hypothalamic Neurogenesis as an Adaptive Metabolic Mechanism

Abstract

In the adult brain, well-characterized neurogenic niches are located in the subventricular zone (SVZ) of the lateral ventricles and in the subgranular zone (SGZ) of the hippocampus. In both regions, neural precursor cells (NPCs) share markers of embryonic radial glia and astroglial cells, and in vitro clonal expansion of these cells leads to neurosphere formation. It has also been more recently demonstrated that neurogenesis occurs in the adult hypothalamus, a brain structure that integrates peripheral signals to control energy balance and dietary intake. The NPCs of this region, termed tanycytes, are ependymal-glial cells, which comprise the walls of the infundibular recess of the third ventricle and contact the median eminence. Thus, tanycytes are in a privileged position to detect hormonal, nutritional and mitogenic signals. Recent studies reveal that in response to nutritional signals, tanycytes are capable of differentiating into orexigenic or anorexigenic neurons, suggesting that these cells are crucial for control of feeding behavior. In this review, we discuss evidence, which suggests that hypothalamic neurogenesis may act as an additional adaptive mechanism in order to respond to changes in diet.

Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche

“…However, the physiological role of NPC proliferation within the hypothalamic stem cell niche in long-term body weight homeostasis including control of feeding and energy balance is intensively discussed in the recent literature. 8,47,48,51,63 In this concept, proliferation of NPCs-mainly NSCs located within the lateral hypothalamus, which are inhibited by NE signaling in our studies-is associated with body weight loss or maintenance, while proliferation of medio-basal NPCs appears to be associated with weight gain. The actions of NE on periventricular neurogenesis are in contrast to its effects on hippocampal neurogenesis with its stimulatory role on NPC proliferation within the SGZ of the dentate gyrus (our study and those of others 14,15 ).…”

“…47 This parenchymal hypothalamic neurogenesis has been reported to be regulated by several cytokines or neurotrophic factors as well as by specific neurodegenerative events and dietary signals. 47,48 The relationship between these parenchymal hypothalamic NPCs and those of the hypothalamic ventricular zone remains unclear, but might be similar to other brain regions with ventricular NPCs (tanycytes in the hypothalamus) might give rise to parenchymal NPCs. 49,50 However, our results provide strong evidence that NE acts as an endogenous negative regulator of the hypothalamic periventricular stem cell niche, with no or only minor effects on ependymal tanycytes.…”

Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting eating behavior

“…Thus, due to their localization in the hypothalamus, tanycytes are in a privileged position to detect hormonal, nutritional and mitogenic signals released by peripheral organs or present in the CSF. Recent studies reveal that in response to nutritional signals, tanycytes are capable of differentiating into anorexigenic neurons (Gouaze et al, 2013; Recabal et al, 2017), which strongly supports the notion that these cells are involved in the control of feeding behavior.…”

“…GLUT2 was found in neurons and astrocytes dispersed in many structures, including the hypothalamus, the brain stem, the thalamic area (Arluison, Quignon, Thorens, Leloup, & Penicaud, 2004; Labouebe, Boutrel, Tarussio, & Thorens, 2016) and in tanycytes (Garcia et al, 2003). Tanycytes are radial glial‐like cells surrounding the lateral walls of the infundibular recess (Recabal, Caprile, & Garcia‐Robles, 2017). Their apical poles contact the cerebrospinal fluid (CSF), and basal extensions project into the arcuate nucleus (AN) (Flament‐Durand & Brion, 1985).…”

Both NPY-Expressing and CART-Expressing Neurons Increase Energy Expenditure and Trabecular Bone Mass in Response to AP1 Antagonism, But Have Opposite Effects on Bone Resorption

“…Although several mechanisms, such as changes in firing activity or in gene expression profiles can be affected, altered neurogenesis is another possible mechanism because ΔFosB was previously shown to increase dendrite spine plasticity, which serve to increase the number of possible contacts between neurons. Indeed, cumulative research over the past two decades demonstrated that neurogenesis occurs in adult human and mouse hypothalamus and is subject to regulation by dietary and other factors . Therefore, to determine whether ΔFosB affected neurogenesis in our experimental models, primary hypothalamic neurons were isolated from adult NPY‐CRE and CART‐CRE mice, infected with CRE‐inducible AP1 factor LVs, thereby targeting only NPY‐producing or CART‐producing neurons in vitro, and neurite regeneration from neurospheres was monitored.…”