奥氮平改变了大鼠海马和纹状体中天冬氨酸相关酶的表达：CBS 和 HO-2。
Olanzapine alters the expression of gasotransmitter-related enzymes: CBS and HO-2 in the rat hippocampus and striatum.
机构信息
Department of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Ul. Medyków18, 40-752, Katowice, Poland.
Department and Clinic of Psychiatric Rehabilitation, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Ul. Ziołowa 45/47, 40-635, Katowice, Poland.
出版信息
Pharmacol Rep. 2023 Dec;75(6):1610-1618. doi: 10.1007/s43440-023-00538-5. Epub 2023 Oct 24.
BACKGROUND
Gaseous neurotransmitters have been thought to be novel factors involved in the mechanisms of mental disorders pathogenesis for quite some time. However, little is known about the potential crosstalk between neuronal gasotransmitter signaling and neuroleptics action. The present work was, therefore, focused on gene expression of HS and CO-producing enzymes in the brains of rats chronically treated with olanzapine, an atypical antipsychotic drug.
METHODS
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 a dose of 5 mg/kg daily). All individuals were sacrificed under anesthesia and the whole brains excised. Immunohistochemical procedure was used for histological assessment of the whole brain and for quantitative analysis of cystathionine β-synthase (CBS) and heme oxygenase 2 (HO-2) protein distribution in selected brain structures.
RESULTS
Long-term treatment with olanzapine is reflected in different changes in the number of enzymes-expressing cells in the rat brain. Olanzapine decreased the number of CBS-expressing cells and possibly reduced HS synthesis in the hippocampus and striatum. The antipsychotic administration increased the number of HO-2 immunopositive cells and probably stimulated the CO production in the hippocampus.
CONCLUSIONS
Modulatory effect of olanzapine on cellular mechanisms of gasotransmitter synthesis may be an alternative way of their pharmacological action.
背景
一段时间以来，人们一直认为气态神经递质是参与精神障碍发病机制的新型因素。然而，关于神经元气体信号转导与神经安定药作用之间的潜在串扰知之甚少。因此，本工作集中研究了慢性给予奥氮平（一种新型抗精神病药物）的大鼠脑中 HS 和 CO 生成酶的基因表达。
方法
研究对象为成年雄性 Sprague-Dawley 大鼠，分为两组：对照组和实验组，实验组大鼠接受奥氮平（28 天腹腔注射，剂量为 5mg/kg/天）。所有个体均在麻醉下处死，并取出整个大脑。免疫组织化学程序用于整个大脑的组织学评估以及半胱氨酸β-合酶（CBS）和血红素加氧酶 2（HO-2）蛋白在选定脑结构中的分布的定量分析。
结果
长期接受奥氮平治疗会导致大鼠大脑中表达酶的细胞数量发生不同变化。奥氮平减少了 CBS 表达细胞的数量，并可能减少了海马体和纹状体中的 HS 合成。抗精神病药物治疗增加了 HO-2 免疫阳性细胞的数量，并可能刺激了海马体中的 CO 生成。
结论
奥氮平对气体递质合成细胞机制的调节作用可能是其药理学作用的另一种方式。
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