Identification of Sox2 and NeuN Double-Positive Cells in the Mouse Hypothalamic Arcuate Nucleus and Their Reduction in Number With Aging.

Ayumu Sugiura,Shin Kedashiro,Takeshi Kameyama,Yoshimi Takai,Tatsuhiro Shimizu,Muneaki Miyata,Tomohiko Maruo,Kiyohito Mizutani

doi:10.3389/fnagi.2020.609911

Abstract

The hypothalamus plays a central role in homeostasis and aging. The hypothalamic arcuate nucleus (ARC) controls homeostasis of food intake and energy expenditure and retains adult neural stem cells (NSCs)/progenitor cells. Aging induces the loss of NSCs and the enhancement of inflammation, including the activation of glial cells in the ARC, but aging-associated alterations of the hypothalamic cells remain obscure. Here, we identified Sox2 and NeuN double-positive cells in a subpopulation of cells in the mouse ARC. These cells were reduced in number with aging, although NeuN-positive neuronal cells were unaltered in the total number. Diet-induced obesity mice fed with high-fat diet presented a similar hypothalamic alteration to aged mice. This study provides a new insight into aging-induced changes in the hypothalamus.

Highlights

Aging is one of the biggest issues that human beings have been tackling
The cells estimated by nuclear staining with DAPI in the arcuate nucleus (ARC) were unaltered in total number with aging (Figure 1C), but Sox2-positive cells were significantly reduced in number in aged mice (Figures 1D,E)
These results suggest that Sox2-positive cells in the parenchyma of the ARC are reduced in number with aging as described for the tanycytes (Zhang et al, 2017)

Summary

Introduction

Studies using various model organisms from yeast, a unicellular eukaryote, to rhesus monkey, a primate, have characterized aging, including genome instability, telomere shortage, mitochondrial dysfunction, and so on (López-Otín et al, 2013). The extension of a healthy life span is an important subject for both natural science and economy. Despite numerous studies, it appears that only caloric restriction succeeds in extending the life span of model organisms and humans (Klass, 1977; Weindruch et al, 1986; Chippindale et al, 1993; Lin et al, 2000; Colman et al, 2009). Recent studies have revealed that signaling pathways, such as the insulin-like growth factor pathway, are associated with the effects of caloric restriction (Lakowski and Hekimi, 1998; Vitale et al, 2019), but it is largely unknown how caloric restriction delays natural aging or induces the hormesis effect

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Conclusion