Oestradiol and diet modulate energy homeostasis and hypothalamic neurogenesis in the adult female mouse.

Oestradiol and diet modulate energy homeostasis and hypothalamic neurogenesis in the adult female mouse.
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DOI:
10.1111/jne.12206
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发表时间:
2014-11
影响因子:
3.2
通讯作者:
Tetel MJ
Tetel MJ
中科院分区:
医学3区
文献类型:
--
作者:
Bless EP;Reddy T;Acharya KD;Beltz BS;Tetel MJ

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瘦素和雌二醇在能量平衡和生育方面具有重叠的功能,并且这些激素的受体位于相同的下丘脑区域。虽然,历史上,它被认为是成年哺乳动物的神经发生仅限于嗅球和海马,最近的研究发现,新的神经元在雄性啮齿动物下丘脑。此外,这些新的神经元中的一些是瘦素敏感的,并受到饮食的影响。在本研究中,我们测试的假设,饮食和激素状态调节成年雌性小鼠下丘脑神经发生。切除成年小鼠卵巢并植入含有雌二醇(E2)或油的胶囊。在每组中,小鼠喂食高脂肪饮食(HFD)或维持标准食物(STND)。所有动物静脉注射5-溴-2 ′-脱氧尿苷(BrdU)9天,34天后注射瘦素诱导活化和转录信号转导子3(pSTAT 3)磷酸化后处死。脑组织用BrdU(新生细胞)、Hu(神经元标记物)和pSTAT 3(瘦素敏感性)进行化学标记。虽然HFD小鼠变得肥胖,但雌二醇可防止肥胖。饮食和激素对弓状核、腹内侧下丘脑和背内侧下丘脑中的新细胞(BrdU+)存在强烈的相互作用。HFD增加了新细胞的数量,而E2抑制了这种作用。相反,E2增加了STND饮食小鼠所有下丘脑区域的新细胞数量。虽然在下丘脑中发现的新的瘦素敏感神经元(BrdU-Hu-pSTAT 3)的总数很低,但HFD增加了弓状核中的这些新细胞,而E2减弱了这种诱导。这些结果表明,成年神经发生在下丘脑神经原性龛调制饮食和激素状态,并与能量稳态雌性小鼠。
Leptin and oestradiol have overlapping functions in energy homeostasis and fertility, and receptors for these hormones are localised in the same hypothalamic regions. Although, historically, it was assumed that mammalian adult neurogenesis was confined to the olfactory bulbs and the hippocampus, recent research has found new neurones in the male rodent hypothalamus. Furthermore, some of these new neurones are leptin-sensitive and affected by diet. In the present study, we tested the hypothesis that diet and hormonal status modulate hypothalamic neurogenesis in the adult female mouse. Adult mice were ovariectomised and implanted with capsules containing oestradiol (E2) or oil. Within each group, mice were fed a high-fat diet (HFD) or maintained on standard chow (STND). All animals were administered i.c.v. 5-bromo-2′-deoxyuridine (BrdU) for 9 days and sacrificed 34 days later after an injection of leptin to induce phosphorylation of signal transducer of activation and transcription 3 (pSTAT3). Brain tissue was immunohistochemically labelled for BrdU (newly born cells), Hu (neuronal marker) and pSTAT3 (leptin sensitive). Although mice on a HFD became obese, oestradiol protected against obesity. There was a strong interaction between diet and hormone on new cells (BrdU+) in the arcuate, ventromedial hypothalamus and dorsomedial hypothalamus. HFD increased the number of new cells, whereas E2 inhibited this effect. Conversely, E2 increased the number of new cells in mice on a STND diet in all hypothalamic regions studied. Although the total number of new leptin-sensitive neurones (BrdU-Hu-pSTAT3) found in the hypothalamus was low, HFD increased these new cells in the arcuate, whereas E2 attenuated this induction. These results suggest that adult neurogenesis in the hypothalamic neurogenic niche is modulated by diet and hormonal status and is related to energy homeostasis in female mice.
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