Ziarniak Kamil, Kołodziejski Paweł A, Pruszyńska-Oszmałek Ewa, Dudek Monika, Kalló Imre, Śliwowska Joanna H
Laboratory of Neurobiology, Faculty of Veterinary Medicine and Animal Science, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznan, Poland.
Department of Animal Physiology, Biochemistry and Biostructure, Faculty of Veterinary Medicine and Animal Science, Poznan University of Life Sciences, Wolynska 35, 60-637 Poznan, Poland.
Neuroscience. 2020 Dec 15;451:184-196. doi: 10.1016/j.neuroscience.2020.10.003. Epub 2020 Oct 14.
KNDy neurons co-expressing kisspeptin (KP), neurokinin B (NKB) and dynorphin A (DYN A) in the arcuate nucleus of the hypothalamus (ARC) are key regulators of reproduction. Their activity is influenced by metabolic and hormonal signals. Previously, we have shown that orchidectomy alters the KP-, NKB-, and DYN A-immunoreactivity in the high-fat diet-induced (HFD) obesity and diabetes type 2 (DM2) models. Considering the potential sex difference in the response of KNDy neurons, we have hypothesized that ovariectomy (OVX) and post-ovariectomy replacement with estradiol (OVX+E) or estradiol and progesterone (OVX+E+P) will also affect these neurons in HFD and DM2 females. Thus, each of these treatment protocols were employed for control, HFD, and DM2 groups of rats leading to nine experimental conditions within which we have determined the number of KP-, NKB-, or DYN-immunoreactive (-ir) neurons and assessed the metabolic and hormonal profiles of the animals. Accordingly: (1) no effects of group and surgery were observed on the number of KP-ir neurons; (2) the overall number of NKB-ir neurons was higher in the OVX+E+P and OVX+E animals compared to OVX; (3) overall, the number of DYN A-ir neurons was higher in DM2 vs. control group, and surgery had an effect on the number of DYN A-ir neurons; (4) the metabolic and hormonal profiles were altered in HFD and DM2 animals compared to controls. Current data together with our previously published results indicate sex-specific differences in the response of KNDy neurons to DM2.
在下丘脑弓状核（ARC）中共同表达亲吻素（KP）、神经激肽B（NKB）和强啡肽A（DYN A）的KNDy神经元是生殖的关键调节因子。它们的活动受代谢和激素信号影响。此前，我们已表明，在高脂饮食诱导的（HFD）肥胖和2型糖尿病（DM2）模型中，去势会改变KP、NKB和DYN A的免疫反应性。考虑到KNDy神经元反应中可能存在的性别差异，我们推测，卵巢切除术（OVX）以及卵巢切除术后用雌二醇（OVX+E）或雌二醇和孕酮（OVX+E+P）替代治疗，也会影响HFD和DM2雌性大鼠的这些神经元。因此，将这些治疗方案分别应用于大鼠的对照组、HFD组和DM2组，产生了九个实验条件，在此条件下我们确定了KP、NKB或DYN免疫反应性（-ir）神经元的数量，并评估了动物的代谢和激素水平。结果如下：（1）未观察到分组和手术对KP-ir神经元数量有影响；（2）与OVX组相比，OVX+E+P组和OVX+E组中NKB-ir神经元的总数更多；（3）总体而言，DM2组中DYN A-ir神经元的数量高于对照组，且手术对DYN A-ir神经元的数量有影响；（4）与对照组相比，HFD和DM2动物的代谢和激素水平发生了改变。目前的数据以及我们之前发表的结果表明，KNDy神经元对DM2的反应存在性别特异性差异。
