Department of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, ul. Medyków Street 18, 40-752, Katowice, Poland.
Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, 67, Via Roma, 56100, Pisa, Italy.
Pharmacol Rep. 2021 Aug;73(4):1188-1194. doi: 10.1007/s43440-021-00267-7. Epub 2021 Apr 29.
Phoenixin, spexin and nesfatin-1 belong to a family of newly discovered multifunctional neuropeptides that play regulatory roles in several brain structures and modulate the activity of important neural networks. However, little is known about their expression and action at the level of brainstem. The present work was, therefore, focused on gene expression of the aforementioned peptides in the brainstem of rats chronically treated with olanzapine, a second generation antipsychotic drug.
Studies were carried out on adult, male Sprague-Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28-day-long intraperitoneal injection, at dose 5 mg/kg daily). All individuals were killed under anesthesia and the brainstem excised. Total mRNA was isolated from homogenized samples of both structures and the RT-PCR method was used for estimation of related SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expression.
Long-term treatment with olanzapine is reflected in qualitatively different changes in expression of examined neuropeptides mRNA in the rat brainstem. Olanzapine significantly decreased NPQ/spexin mRNA expression, but increased SMIM20/phoenixin mRNA level in the rat brainstem; while NUCB2/nesfatin-1 mRNA expression remained unchanged.
Olanzapine can affect novel peptidergic signaling in the rat brainstem. This may cautiously suggest the presence of an alternative mode of its action.
凤凰素、斯佩辛和 nesfatin-1 属于一组新发现的多功能神经肽家族，它们在大脑的几个结构中发挥调节作用，并调节重要神经网络的活动。然而，它们在脑干水平的表达和作用知之甚少。因此，本工作主要集中在慢性给予奥氮平（第二代抗精神病药物）的大鼠脑干中上述肽的基因表达。
研究对象为成年雄性 Sprague-Dawley 大鼠，分为对照组和实验组，实验组用奥氮平（28 天腹腔注射，剂量为 5mg/kg 每日）处理。所有个体在麻醉下处死，取出脑干。从两个结构的匀浆样本中分离总 mRNA，并使用 RT-PCR 方法估计相关 SMIM20/凤凰素、NPQ/斯佩辛和 NUCB2/nesfatin-1 基因表达。
长期用奥氮平处理反映了在大鼠脑干中检测到的神经肽 mRNA 表达发生了质的不同变化。奥氮平显著降低了 NPQ/斯佩辛 mRNA 的表达，但增加了大鼠脑干中 SMIM20/凤凰素 mRNA 的水平；而 NUCB2/nesfatin-1 mRNA 的表达保持不变。
奥氮平可能会影响大鼠脑干中的新型肽能信号转导。这可能谨慎地表明其存在替代作用模式。
