Gok Yurtseven Duygu, Serter Kocoglu Sema, Minbay Zehra, Eyigor Ozhan
Department of Histology and Embryology, Bursa Uludag University Institute of Health Science, Bursa 16240, Turkey.
Department of Histology and Embryology, Balikesir University School of Medicine, Balikesir 10145, Turkey.
Brain Sci. 2020 Sep 11;10(9):630. doi: 10.3390/brainsci10090630.
Nesfatin-1, identified as an anorexigenic peptide, regulates the energy metabolism by suppressing food intake. The majority of nesfatin-1-synthesizing neurons are concentrated in various hypothalamic nuclei, especially in the supraoptic (SON), arcuate (ARC) and paraventricular nuclei (PVN). We tested the hypothesis that the glutamatergic system regulates nesfatin-1 neurons through glutamate receptors. Therefore, the first aim of the proposed studies was to examine effects of different glutamate agonists in the activation of nesfatin-1 neurons using c-Fos double immunohistochemical labeling. Experimental groups were formed containing male and female rats which received intraperitoneal injections of glutamate agonists kainic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) while the control rats received vehicle. The significant increase in the number of c-Fos-expressing nesfatin-1 neurons after agonist injections were observed both in female and male subjects and some of these effects were found to be sexually dimorphic. In addition, treatment with specific glutamate antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or dizocilpine (MK-801) before each of the three agonist injections caused a statistically significant reduction in the number of activated nesfatin-1 neurons in the hypothalamic nuclei including supraoptic, paraventricular and arcuate nuclei. The second aim of the study was to determine the expression of glutamate receptor subunit proteins in the nesfatin-1 neurons by using a double immunofluorescence technique. The results showed that the glutamate receptor subunits, which may form homomeric or heteromeric functional receptor channels, were expressed in the nesfatin-1 neurons. In conclusion, the results of this study suggest that nesfatin-1 neurons respond to glutamatergic signals in the form of neuronal activation and that the glutamate receptors that are synthesized by nesfatin-1 neurons may participate in the glutamatergic regulation of these neurons.
Nesfatin-1作为一种厌食肽，通过抑制食物摄入来调节能量代谢。大多数合成nesfatin-1的神经元集中在各种下丘脑核团中，尤其是视上核（SON）、弓状核（ARC）和室旁核（PVN）。我们检验了谷氨酸能系统通过谷氨酸受体调节nesfatin-1神经元的假说。因此，本研究的首要目的是利用c-Fos双重免疫组织化学标记法，检测不同谷氨酸激动剂对nesfatin-1神经元激活的影响。将雄性和雌性大鼠分为实验组，腹腔注射谷氨酸激动剂海藻酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和N-甲基-D-天冬氨酸（NMDA），而对照组大鼠注射赋形剂。在雄性和雌性大鼠中均观察到激动剂注射后c-Fos表达的nesfatin-1神经元数量显著增加，且其中一些效应存在性别差异。此外，在三次激动剂注射前分别用特异性谷氨酸拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）或地卓西平（MK-801）处理，导致下丘脑核团（包括视上核、室旁核和弓状核）中激活的nesfatin-1神经元数量在统计学上显著减少。本研究的第二个目的是利用双重免疫荧光技术，确定nesfatin-1神经元中谷氨酸受体亚基蛋白的表达。结果显示，可能形成同聚体或异聚体功能受体通道的谷氨酸受体亚基在nesfatin-1神经元中表达。总之，本研究结果表明，nesfatin-1神经元以神经元激活的形式对谷氨酸能信号作出反应，且nesfatin-1神经元合成的谷氨酸受体可能参与这些神经元的谷氨酸能调节。
