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Time-Dependent Changes in the Serum Levels of Neurobiochemical Factors After Acute Methadone Overdose in Adolescent Male Rat.
Cellular and Molecular Neurobiology ( IF 4 ) Pub Date : 2020-07-25 , DOI: 10.1007/s10571-020-00931-1
Leila Ahmad-Molaei 1 , Mahsa Pourhamzeh 2 , Reza Ahadi 2 , Fariba Khodagholi 1 , Hossein Hassanian-Moghaddam 3, 4 , Abbas Haghparast 1
Affiliation  

Acute methadone toxicity is a major public health concern which has adverse effects on brain tissue and results in recurrent or delayed respiratory arrest. Our study aimed to investigate the time-dependent changes in several serum biochemical markers of brain damage, spatial working memory, and the brain tissue following acute methadone overdose. Adolescent male rats underwent an intraperitoneal (i.p.) injection of 15 mg/kg methadone. In case of apnea occurrence, resuscitation was performed by a ventilatory pump and administrating naloxone (2 mg/kg; i.p.). The animals were classified into groups of treated rats; methadone and naloxone-Apnea (M/N-Apnea), M/N-Sedate, Methadone, Naloxone, and control (saline) groups. The serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein factors, and (Lactate/Pyruvate) L/P ratio were evaluated at the time-points of 6, 24, and 48 h (h). We found that the alterations of S100B and L/P ratio were considerable in the M/N-Apnea and Methadone groups from the early hours post-methadone overdose, while NSE serum levels elevation was observed only in M/N-Apnea group with a delay at 48 h. Further, we assessed the spatial working memory (Y-maze test), morphological changes, and neuronal loss. The impaired spontaneous alternation behavior was detected in the M/N-Apnea groups on days 5 and 10 post-methadone overdose. The morphological changes of neurons and the neuronal loss were detectable in the CA1, striatum, and cerebellum regions, which were pronounced in both M/N-Apnea and Methadone groups. Together, our findings suggest that alterations in the serum levels of S100B and NSE factors as well as L/P ratio could be induced by methadone overdose with the presence or absence of apnea before the memory impairment and tissue injury in adolescent male rats.



中文翻译:

青春期雄性大鼠急性美沙酮过量后血清神经生化因子水平的时间依赖性变化。

急性美沙酮毒性是一个主要的公共卫生问题,它对脑组织有不利影响,并导致反复或延迟呼吸停止。我们的研究旨在调查急性美沙酮过量后脑损伤、空间工作记忆和脑组织的几种血清生化标志物的时间依赖性变化。青春期雄性大鼠接受了 15 mg/kg 美沙酮的腹膜内 (ip) 注射。在发生呼吸暂停的情况下,通过呼吸泵进行复苏并给予纳洛酮(2 mg/kg;ip)。将动物分为治疗大鼠组;美沙酮和纳洛酮呼吸暂停 (M/N-Apnea)、M/N-镇静剂、美沙酮、纳洛酮和对照组(生理盐水)。S100B、神经元特异性烯醇化酶 (NSE)、髓鞘碱性蛋白因子和 (乳酸/丙酮酸) 的血清水平在 6、24 和 48 h (h) 的时间点评估L / P比。我们发现 S100B 和L / P的变化从美沙酮过量后的早期开始,M/N-呼吸暂停组和美沙酮组的比例相当大,而仅在 M/N-呼吸暂停组中观察到 NSE 血清水平升高,延迟至 48 小时。此外,我们评估了空间工作记忆(Y 迷宫测试)、形态变化和神经元损失。在美沙酮过量后第 5 天和第 10 天,在 M/N 呼吸暂停组中检测到受损的自发交替行为。在 CA1、纹状体和小脑区域可检测到神经元的形态学变化和神经元丢失,这在 M/N 呼吸暂停组和美沙酮组中都很明显。总之,我们的研究结果表明 S100B 和 NSE 因子以及L / P的血清水平的改变在青春期雄性大鼠记忆障碍和组织损伤之前,美沙酮过量与呼吸暂停的存在或不存在可诱导比率。

更新日期:2020-07-26
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