Sham controls differed only in that they did not receive a direct radiation beam and CT scan, but instead remained in the anesthesia chamber. One mouse from the treatment and one from the control group were then anesthetized using isoflurane gas. We report that high fat diet HFD selectively activates neurogenesis in the median eminence ME of young adult female but not male mice, and that focal irradiation of the ME in HFD-fed mice reduces weight gain in females but not males. Heating pad set in the low setting was prepared for postoperative treatment of the mice. Dietary change to HFD was initiated at 5. Sections were scored for double labeling by manual examination of optical slices.
A detailed video and protocol describing this focal irradiation methodology is available online Lee et al. In the hypothalamic median eminence ME , tanycytes are a convincing neurogenic source for the arcuate nucleus ArcN and ME. Our data suggest that adult-generated neurons in both hypothalamic regions may show differing sensitivities to dietary and hormonal signals that help maintain energy homeostasis. Post-hoc testing showed that significantly different levels of neurogenesis between ME and ArcN were observed in females [ME 0. Such differences likely at least partially account for differences in the levels and diet-dependence of adult hypothalamic neurogenesis observed by different groups Table 2. The age of the mice used for these studies has ranged from early postnatal Lee et al. The results of the studies employing cell lineage analysis to identify putative neural progenitor cell types in the postnatal hypothalamus are summarized in Table 1. The hippocampal dentate gyrus and the subventricular zone of the lateral ventricles are canonical neurogenic niches. These observations suggest that the differential region-specific changes in neurogenesis may lead to differential generation of orexinergic Supplementary Figures 1D,F and anorexinergic neurons Supplementary Figures 1E,G in response to dietary cues, and may serve as a mechanism that allows adaptation to long-term changes in energy balance homeostasis. We investigated how changes in diet can modulate hypothalamic neurogenesis by presenting young adult mice with contrasting diets. Supplementary Material The Supplementary Material for this article can be found online at: Sham controls differed only in that they did not receive a direct radiation beam and CT scan, but instead remained in the anesthesia chamber. After three days, BrdU was injected intraperitoneally twice per day for 9 days. Tanycytes of the hypothalamic ventricular zone have also been reported to act as neural progenitors Xu et al. The increased neurogenesis in adult female ME may serve to replace damaged neurons in this region. As a consequence to this radiological treatment, we observe alterations in weight gain in a subset of irradiated mice compared to sham controls, with reduced HFD-induced weight gain in females, but not in males Figure 3C. Weights were taken twice a week. Three days later, mice were divided into treatment and sham control groups and weighed. To clarify the extent to which sex-dependent factors might regulate neurogenesis in different hypothalamic regions, we investigated levels of hypothalamic neurogenesis in both the arcuate nucleus ArcN and ME in male and female young adult mice fed normal chow and HFD. For the ME, the dorsal-ventral boundary of the cells counted was the third ventricle 3V floor and the ventral edge of the external layer of the ME. We set out to test whether additional dietary conditions could also alter neurogenesis in the ME, and whether these led to comparable changes in neurogenesis in the arcuate nucleus ArcN , which lies inside the blood-brain barrier within the hypothalamus proper. Mice received either a high fat diet ad libitum at 5. In contrast, all tanycyte subtypes directly contact the CSF, and can potentially respond to intracerebral ventricular signals Bennett et al. For instance, using a combination of in vitro cell culture and in vivo genetic lineage analysis, it has been claimed that a population of Sox2-positive Li et al. Taken together with our results, this body of work highlights the importance of examining both the regional differences in hypothalamic neurogenesis and the sex-specific differences. High-fat diet HFD has been reported to constitutively inhibit neurogenesis in the mediobasal hypothalamic parenchyma Li et al.
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