关键词: Animal models Forced swimming test Long-term sequelae Neuroinflammation Phenethylamine Sepsis-associated encephalopathy

Mesh : Animals Rats, Wistar Male Sepsis / complications drug therapy metabolism psychology Depression / drug therapy etiology Rats Hallucinogens / pharmacology therapeutic use Phenethylamines / pharmacology therapeutic use Prefrontal Cortex / drug effects metabolism Sepsis-Associated Encephalopathy / drug therapy metabolism

来  源:   DOI:10.1016/j.neulet.2024.137845

Abstract:
Sepsis-associated encephalopathy, which manifests in severe cognitive and depressive symptoms, is directly linked to neuroinflammation. Our study investigates the efficacy of 25H-NBOMe, a phenethylamine, in alleviating these symptoms, potentially offering an innovative treatment for post-sepsis depression. Wistar rats, weighing between 250-300 g, were subjected to cecal ligation and puncture (CLP) surgery to induce sepsis. Depressive-like behaviors were assessed using the forced swim test (FST) on either day 7 or 14 post-surgery, to establish the presence of depressive symptoms. The impact of 25H-NBOMe treatment was then evaluated, focusing on the head-twitch response (HTR), performance in the FST, and GFAP expression in the prefrontal cortex. Treatment with 25H-NBOMe resulted in significant behavioral changes, demonstrated by decreased immobility and increased swimming times in the FST, along with a rise in the HTR. These outcomes indicate a reduction in depressive-like symptoms post-sepsis and the psychoactive effects of the compound. Furthermore, a notable decrease in GFAP expression in the study highlights the compound\'s impact on mitigating sepsis-induced astrogliosis. This study demonstrates the effectiveness of 25H-NBOMe, a psychedelic in the phenethylamine class, in treating post-sepsis depression and reducing astrogliosis. However, the psychedelic nature of 25H-NBOMe calls for further investigation into similar compounds with less psychoactive impact, crucial for advancing treatment options for neuropsychiatric symptoms following sepsis.
摘要:
脓毒症相关性脑病,表现为严重的认知和抑郁症状,与神经炎症直接相关。我们的研究调查了25H-NBOMe的疗效,苯乙胺,为了减轻这些症状,可能为脓毒症后抑郁症提供创新的治疗方法。Wistar大鼠,重量在250-300克之间,进行盲肠结扎和穿刺(CLP)手术以诱发脓毒症。在手术后第7天或第14天使用强迫游泳测试(FST)评估抑郁样行为,确定抑郁症状的存在。然后评估25H-NBOMe治疗的影响,专注于头部抽搐反应(HTR),在FST中的表现,和GFAP在前额叶皮层的表达。25H-NBOMe治疗导致显著的行为改变,FST中的不活动减少和游泳时间增加,随着HTR的上升。这些结果表明脓毒症后抑郁样症状的减少和化合物的精神活性作用。此外,研究中GFAP表达的显著下降凸显了该化合物对减轻脓毒症诱导的星形胶质细胞增生的影响.这项研究证明了25H-NBOMe的有效性,苯乙胺类的迷幻药,在治疗脓毒症后抑郁和减少星形胶质细胞增生方面。然而,25H-NBOMe的迷幻性质需要进一步研究类似的化合物,其精神影响较小,对于推进脓毒症后神经精神症状的治疗方案至关重要。
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