Poon Kinning, Barson Jessica R, Shi Huanzhi, Chang Guo Qing, Leibowitz Sarah F
Laboratory of Behavioral Neurobiology, Rockefeller UniversityNew York, NY, USA.
Department of Neurobiology and Anatomy, Drexel University College of MedicinePhiladelphia, PA, USA.
Front Behav Neurosci. 2017 May 17;11:91. doi: 10.3389/fnbeh.2017.00091. eCollection 2017.
Exposure to a high fat diet (HFD) during gestation stimulates neurogenesis and expression of hypothalamic orexigenic neuropeptides that affect consummatory and emotional behaviors. With recent studies showing a HFD to increase inflammation, this report investigated the neuroinflammatory chemokine, CXCL12, and compared the effects of prenatal CXCL12 injection to those of prenatal HFD exposure, first, by testing whether the HFD affects circulating CXCL12 in the dam and the CXCL12 system in the offspring brain, and then by examining whether prenatal exposure to CXCL12 itself mimics the effects of a HFD on hypothalamic neuropeptides and emotional behaviors. Our results showed that prenatal exposure to a HFD significantly increased circulating levels of CXCL12 in the dam, and that daily injections of CXCL12 induced a similar increase in CXCL12 levels as the HFD. In addition, prenatal HFD exposure significantly increased the expression of CXCL12 and its receptors, CXCR4 and CXCR7, in the hypothalamic paraventricular nucleus (PVN) of the offspring. Finally, the results revealed strong similarities in the effects of prenatal HFD and CXCL12 administration, which both stimulated neurogenesis and enkephalin (ENK) expression in the PVN, while having inconsistent or no effect in other regions of the hypothalamus, and also increased anxiety as measured by several behavioral tests. These results focus attention specifically on the CXCL12 chemokine system in the PVN of the offspring as being possibly involved in the stimulatory effects of prenatal HFD exposure on ENK-expressing neurons in the PVN and their associated changes in emotional behavior.
孕期高脂饮食（HFD）会刺激神经发生以及下丘脑促食欲神经肽的表达，进而影响进食和情绪行为。近期研究表明高脂饮食会加剧炎症，本报告对神经炎性趋化因子CXCL12展开研究，并比较产前注射CXCL12与产前暴露于高脂饮食的影响。首先，检测高脂饮食是否会影响母鼠体内循环的CXCL12以及子代大脑中的CXCL12系统；然后，研究产前暴露于CXCL12本身是否会模拟高脂饮食对下丘脑神经肽和情绪行为的影响。我们的结果显示，产前暴露于高脂饮食会显著提高母鼠体内循环的CXCL12水平，每日注射CXCL12也会使CXCL12水平出现与高脂饮食类似的升高。此外，产前高脂饮食暴露会显著增加子代下丘脑室旁核（PVN）中CXCL12及其受体CXCR4和CXCR7的表达。最后，结果显示产前高脂饮食和注射CXCL12的影响具有很强的相似性，二者均刺激了室旁核中的神经发生和脑啡肽（ENK）表达，而对下丘脑其他区域的影响则不一致或无影响，并且通过多项行为测试测量发现二者均增加了焦虑情绪。这些结果特别关注子代室旁核中的CXCL12趋化因子系统，其可能参与产前高脂饮食暴露对室旁核中表达脑啡肽的神经元的刺激作用及其相关的情绪行为变化。
