Majercikova Z, Kiss A
Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
Folia Biol (Praha). 2015;61(3):110-5. doi: 10.14712/fb2015061030110.
Asenapine (ASE) is a novel atypical antipsychotic used in schizophrenia treatment. Here, the effect of ASE on Fos expression in hypocretin (Hcrt) neurons in medial and lateral portions of the lateral hypothalamus (LH) and the effect of chronic unpredictable variable mild stress (CMS) preconditioning were studied. CMS consisted of restraint, social isolation, crowding, swimming, and cold and lasted 21 days. The rats were sacrificed on day 22, 90 min after a single injection of vehicle (saline 300 μl/rat subcutaneously--s.c.) or ASE (0.3 mg/kg s.c.). Control (CON), ASE, CMS, and CMS+ASE groups were used. Fos protein was visualized by the avidin biotin peroxidase technique, while Hcrt perikarya by fluorescent dye. Fos/Hcrt co-localizations were evaluated under parallel light and fluorescent illuminations. In the single Fos expression assessment, the Fos number was significantly higher in the medial in comparison with the lateral LH portion in each group. No differences in Fos amount were observed between the individual groups within the medial and lateral LH portions. In the Fos/Hcrt co-localization assessments, ASE significantly reduced the number of Fos/Hcrt neurons in the medial, but not lateral, LH portion in ASE and CMS+ASE groups. CMS only slightly contributed to the inhibitory effect of ASE in the CMS+ASE groups. The present data show as the first that ASE may reduce the activity of Hcrt cells in the medial LH portion, which might correspond with the relatively low weight gain liability of ASE. CMS preconditioning did not significantly interfere with this impact of ASE.
阿塞那平（ASE）是一种用于治疗精神分裂症的新型非典型抗精神病药物。在此，研究了ASE对下丘脑外侧区（LH）内侧和外侧部分的下丘脑泌素（Hcrt）神经元中Fos表达的影响以及慢性不可预测性温和应激（CMS）预处理的作用。CMS包括束缚、社会隔离、拥挤、游泳、寒冷，持续21天。在第22天，单次注射溶媒（300μl/大鼠皮下注射生理盐水）或ASE（0.3mg/kg皮下注射）90分钟后处死大鼠。使用了对照组（CON）、ASE组、CMS组和CMS + ASE组。通过抗生物素蛋白生物素过氧化物酶技术观察Fos蛋白，用荧光染料观察Hcrt神经元胞体。在平行光和荧光照明下评估Fos/Hcrt共定位。在单一Fos表达评估中，每组内侧LH部分的Fos数量显著高于外侧LH部分。在内侧和外侧LH部分的各个组之间未观察到Fos数量的差异。在Fos/Hcrt共定位评估中，ASE显著减少了ASE组和CMS + ASE组内侧LH部分而非外侧LH部分的Fos/Hcrt神经元数量。在CMS + ASE组中，CMS仅对ASE的抑制作用有轻微贡献。本研究首次表明，ASE可能降低内侧LH部分Hcrt细胞的活性，这可能与ASE相对较低的体重增加倾向相对应。CMS预处理并未显著干扰ASE的这一作用。
