The impact of dexmedetomidine on ketamine-induced neurotoxicity and cognitive impairment in young mice

IF 1.7 4区医学 Q3 DEVELOPMENTAL BIOLOGY International Journal of Developmental Neuroscience Pub Date : 2024-08-27 DOI:10.1002/jdn.10373

Dongdong Chai, Hong Jiang, Xiang Lv

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Abstract

Background

The potential neuroprotective effects of dexmedetomidine against ketamine-induced neurotoxicity remain inconclusive. This study aims to investigate the influence of dexmedetomidine on ketamine-induced neuronal apoptosis and neurodevelopmental toxicity.

Methods

In vitro experiments employed concentrations of 0.1 uM for dexmedetomidine and 50 uM for ketamine individually as well as their combination. Changes in apoptotic proteins and dendritic development in neurons were assessed after a 6-h exposure to the drugs with evaluations conducted 24 hs' post-treatment. In vivo experiments entailed intraperitoneal administration starting from postnatal Day 7 (P7) continuously for 3 days (P7–P9) using dosages of 100 mg/kg for ketamine and 1 mg/kg for dexmedetomidine alone or combined. Learning, memory and motor coordination abilities were evaluated via rotary rod tests and shuttle box experiments at P30 and P60, respectively.

Results

Dexmedetomidine effectively mitigated ketamine-induced apoptosis in hippocampal neurons but did not alleviate associated dendritic developmental abnormalities. Although causing reduced motor coordination in mice, no improvement was observed with regard to this effect or reaction speed when treated with dexmedetomidine alongside ketamine.

Conclusion

This study demonstrates that while dexmedetomidine can mitigate ketamine-induced neuronal apoptosis, it has limited impact on its associated neurodevelopmental toxicities.

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右美托咪定对氯胺酮诱导的幼鼠神经毒性和认知障碍的影响

背景：右美托咪定对氯胺酮诱导的神经毒性的潜在神经保护作用尚无定论。本研究旨在探讨右美托咪定对氯胺酮诱导的神经元凋亡和神经发育毒性的影响：体外实验中，右美托咪定的浓度为 0.1 uM，氯胺酮的浓度为 50 uM。在暴露于药物6小时后，评估神经元凋亡蛋白和树突发育的变化，并在治疗后24小时进行评估。体内实验需要从出生后第7天（P7）开始连续3天（P7-P9）腹腔给药，氯胺酮剂量为100毫克/千克，右美托咪定单独或合并使用的剂量为1毫克/千克。在P30和P60时，分别通过旋转棒测试和穿梭箱实验评估学习、记忆和运动协调能力：结果：右美托咪定能有效缓解氯胺酮诱导的海马神经元凋亡，但不能减轻相关的树突发育异常。虽然右美托咪定会导致小鼠运动协调能力下降，但在使用氯胺酮的同时使用右美托咪定治疗时，并未观察到这种影响或反应速度的改善：本研究表明，虽然右美托咪定可以减轻氯胺酮诱导的神经元凋亡，但对其相关的神经发育毒性影响有限。

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来源期刊

International Journal of Developmental Neuroscience 医学-发育生物学

CiteScore

3.30

自引率

5.60%

发文量

审稿时长

6-12 weeks

期刊介绍： International Journal of Developmental Neuroscience publishes original research articles and critical review papers on all fundamental and clinical aspects of nervous system development, renewal and regeneration, as well as on the effects of genetic and environmental perturbations of brain development and homeostasis leading to neurodevelopmental disorders and neurological conditions. Studies describing the involvement of stem cells in nervous system maintenance and disease (including brain tumours), stem cell-based approaches for the investigation of neurodegenerative diseases, roles of neuroinflammation in development and disease, and neuroevolution are also encouraged. Investigations using molecular, cellular, physiological, genetic and epigenetic approaches in model systems ranging from simple invertebrates to human iPSC-based 2D and 3D models are encouraged, as are studies using experimental models that provide behavioural or evolutionary insights. The journal also publishes Special Issues dealing with topics at the cutting edge of research edited by Guest Editors appointed by the Editor in Chief. A major aim of the journal is to facilitate the transfer of fundamental studies of nervous system development, maintenance, and disease to clinical applications. The journal thus intends to disseminate valuable information for both biologists and physicians. International Journal of Developmental Neuroscience is owned and supported by The International Society for Developmental Neuroscience (ISDN), an organization of scientists interested in advancing developmental neuroscience research in the broadest sense.