Abstract The neuromodulatory effects of brain-derived neurotrophic factor (BDNF) on appetite regulation centre peptide gene activity in the sheep hypothalamus have not been examined yet. The aim of this study was to determine whether BDNF participates in modulation of neuropeptide Y (npy), agouti-related peptide (agrp), cocaine and amphetamine regulated transcript (cart), and proopiomelanocortin (pomc) mRNA expression and selected microRNAs in the sheep hypothalamic arcuate (ARC) nucleus. Animals (Polish Merino sheep, n=24) were divided into three groups. The control group received a central infusion of Ringer-Locke solution (480 µl/day) whereas the experimental groups were treated with BDNF in two doses: 10 or 60 μg/480 µl/day. All sheep received four intracerebroventricular infusions (performed from 08:40 a.m. to 01:30 p.m.; infusion scheme: 4 x 50 min infusions with 30 min intervals between them) on each of three consecutive days. Immediately after the last infusion, the sheep were slaughtered, and selected structures of the hypothalamus were frozen for further real-time qPCR analysis. Central infusion of BDNF evoked dose-dependent changes in npy, agrp, cart, pomc and peptidylglicine alpha-amidating monooxygenase (pam) mRNA expression in the sheep ARC nucleus. An increase in npy, agrp and pomc mRNA expression but also a decrease in cart mRNA expression in the ARC nucleus were detected. Moreover, a decrease in pam (gene encoding an enzyme that converts POMC into α-MSH) mRNA expression, was also noted. Furthermore, after central BDNF administration, changes in miRNA-33a-5p, miRNA-33b-5p, miRNA-377-3p, miRNA-214-3p, miRNA-485 and miRNA-488 expression were observed. Based on the presented results, it can be concluded that BDNF may affect the appetite regulating centre activity through modulation of npy, agrp, cart, pomc and pam mRNA expression in the ARC nucleus. It was also revealed that BDNF modulates miRNA expression in the sheep ARC nucleus.

中文翻译：

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脑源性神经营养因子影响绵羊弓状核食欲调节中枢mRNA和miRNA表达

摘要 脑源性神经营养因子（BDNF）对绵羊下丘脑食欲调节中心肽基因活性的神经调节作用尚未得到研究。本研究的目的是确定 BDNF 是否参与调节神经肽 Y (npy)、刺豚鼠相关肽 (agrp)、可卡因和苯丙胺调节的转录物 (cart) 以及阿黑皮素原 (pomc) mRNA 表达和选定的 microRNAs。下丘脑弓状核（ARC）。动物（波兰美利奴羊，n=24）分为三组。对照组接受中央输注林格-洛克溶液（480 微升/天），而实验组接受两种剂量的 BDNF 治疗：10 或 60 微克/480 微升/天。所有绵羊接受了四次脑室内输注（从上午 08:40 到下午 01:30 进行；输注方案：连续三天输注 4 x 50 分钟，间隔 30 分钟）。在最后一次输注后立即宰杀绵羊，并冷冻选定的下丘脑结构以进行进一步的实时 qPCR 分析。BDNF 的中心输注引起了绵羊 ARC 核中 npy、agrp、cart、pomc 和肽基甘氨酸 α-酰胺化单加氧酶 (pam) mRNA 表达的剂量依赖性变化。检测到 ARC 核中 npy、agrp 和 pomc mRNA 表达增加，但也检测到 car mRNA 表达减少。此外，还注意到pam（编码将POMC 转化为α-MSH 的酶的基因）mRNA 表达降低。此外，在中央 BDNF 给药后，观察到 miRNA-33a-5p、miRNA-33b-5p、miRNA-377-3p、miRNA-214-3p、miRNA-485 和 miRNA-488 表达的变化。基于所呈现的结果，可以得出结论，BDNF 可能通过调节 ARC 核中 npy、agrp、cart、pomc 和 pam mRNA 的表达来影响食欲调节中枢的活动。还发现BDNF调节绵羊ARC细胞核中的miRNA表达。