Osacka J, Horvathova L, Majercikova Z, Kiss Alexander
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Endocr Regul. 2017 Apr 25;51(2):73-83. doi: 10.1515/enr-2017-0007.
Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN) pars compacta (SNC, A8), pars reticulata (SNR, A9), and pars lateralis (SNL), the ventral tegmental area (VTA, A10), the locus coeruleus (LC, A6) and subcoeruleus (sLC), the ventrolateral pons (PON-A5), the nucleus of the solitary tract (NTS-A2), the area postrema (AP), and the ventrolateral medulla (VLM-A1) was quantitatively evaluated aft er a single administration of asenapine (ASE) (designated for schizophrenia treatment) in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS) for 21 days. Th e aim of the present study was to reveal whether a single ASE treatment may 1) activate Fos expression in the brain areas selected; 2) activate tyrosine hydroxylase (TH)-synthesizing cells displaying Fos presence; and 3) be modulated by CMS preconditioning.
Control (CON), ASE, CMS, and CMS+ASE groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. Th e ASE and CMS+ASE groups received a single dose of ASE (0.3 mg/kg, s.c.) and CON and CMS saline (300 μl/rat, s.c.). The animals were sacrificed 90 min aft er the treatments. Fos protein and TH-labeled immunoreactive perikarya were analyzed on double labeled histological sections and enumerated on captured pictures using combined light and fluorescence microscope illumination.
Saline or CMS alone did not promote Fos expression in any of the structures investigated. ASE alone or in combination with CMS elicited Fos expression in two parts of the SN (SNC, SNR) and the VTA. Aside from some cells in the central gray tegmental nuclei adjacent to LC, where a small number of Fos profiles occurred, none or negligible Fos occurrence was detected in the other structures investigated including the LC and sLC, PON-A5, NTS-A2, AP, and VLM-A1. CMS preconditioning did not infl uence the level of Fos induction in the SN and VTA elicited by ASE administration. Similarly, the ratio between the amount of free Fos and Fos colocalized with TH was not aff ected by stress preconditioning in the SNC, SNR, and the VTA.
Th e present study provides an anatomical/functional knowledge about the nature of the acute ASE treatment on the catecholamine-synthesizing neurons activity in certain brain structures and their missing interplay with the CMS preconditioning.
在经21天慢性不可预测性温和应激（CMS）预处理的雄性Wistar大鼠中，单次给予阿塞那平（ASE，用于治疗精神分裂症）后，定量评估黑质致密部（SNC，A8）、黑质网状部（SNR，A9）、黑质外侧部（SNL）、腹侧被盖区（VTA，A10）、蓝斑（LC，A6）和蓝斑下核（sLC）、腹外侧脑桥（PON - A5）、孤束核（NTS - A2）、最后区（AP）以及延髓腹外侧（VLM - A1）中儿茶酚胺合成神经元中的Fos蛋白表达。本研究的目的是揭示单次ASE治疗是否：1）激活所选脑区中的Fos表达；2）激活显示Fos存在的酪氨酸羟化酶（TH）合成细胞；3）受CMS预处理的调节。
使用对照组（CON）、ASE组、CMS组和CMS + ASE组。CMS包括束缚、社会隔离、拥挤、游泳和寒冷刺激。ASE组和CMS + ASE组接受单次剂量的ASE（0.3 mg/kg，皮下注射），CON组和CMS组注射生理盐水（300 μl/只大鼠，皮下注射）。处理后90分钟处死动物。在双标记组织学切片上分析Fos蛋白和TH标记的免疫反应性核周体，并使用组合光和荧光显微镜照明在捕获的图像上计数。
单独给予生理盐水或CMS均未促进所研究的任何结构中的Fos表达。单独使用ASE或与CMS联合使用均在黑质的两个部分（SNC、SNR）和VTA中引发Fos表达。除了与LC相邻的中央灰质被盖核中的一些细胞出现少量Fos阳性反应外，在所研究的其他结构中，包括LC和sLC、PON - A5、NTS - A2、AP和VLM - A1，未检测到或仅有可忽略不计的Fos出现。CMS预处理不影响ASE给药引起的黑质和VTA中Fos诱导水平。同样，在SNC、SNR和VTA中，游离Fos与与TH共定位的Fos数量之比不受应激预处理的影响。
本研究提供了关于急性ASE治疗对某些脑结构中儿茶酚胺合成神经元活动的性质及其与CMS预处理之间缺乏相互作用的解剖学/功能学知识。
