激活多巴胺 D1 受体可挽救 MK-801 新生儿精神分裂症模型的海马突触可塑性和认知障碍

IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Behavioural Brain Research Pub Date : 2024-09-12 DOI:10.1016/j.bbr.2024.115250
Melissa Hernández-Frausto , Emilio J. Galván, Carolina López-Rubalcava
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引用次数: 0

摘要

精神分裂症是一种在成年早期认知能力下降较快的疾病,会导致外显记忆的保持能力受损。然而,认知障碍的生理和行为功能以及改善和提高认知能力的潜在机制尚不清楚。在这项研究中,我们使用了 MK-801 神经发育性精神分裂症样模型。大鼠分为两组:一组接受 MK-801,另一组连续五天(出生后 7-11 天,PND)接受生理盐水。我们使用急性海马切片的细胞外场记录和巴恩斯迷宫任务评估了青春期早期和青年期的突触可塑性晚期LTP和空间记忆巩固。接下来,我们研究了 D1 受体(D1R)激活作为一种改善认知障碍的机制。我们的研究结果表明,MK-801新生儿治疗会诱导晚期LTP表达受损,并在青春期早期诱导空间记忆检索缺陷,这种缺陷会一直维持到青年期。此外,我们还发现,激活多巴胺 D1R 可改善认知障碍,促进晚期 LTP 的强健表达,并提高巴恩斯迷宫任务的表现,这表明 MK-801 在治疗精神分裂症认知障碍方面具有新颖而潜在的治疗作用。
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Dopamine D1 receptors activation rescues hippocampal synaptic plasticity and cognitive impairments in the MK-801 neonatal schizophrenia model

Schizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model. Rats were divided into two groups: one received MK-801, and the other received saline for five consecutive days (7–11 postnatal days, PND). We evaluated synaptic plasticity late-LTP and spatial memory consolidation in early adolescence and young adulthood using extracellular field recordings in acute hippocampal slices and the Barnes maze task. Next, we examined D1 receptor (D1R) activation as a mechanism to ameliorate cognitive impairments. Our results suggest that MK-801 neonatal treatment induces impairment in late-LTP expression and deficits in spatial memory retrieval in early adolescence that is maintained until young adulthood. Furthermore, we found that activation of dopamine D1R ameliorates the impairments and promotes a robust expression of late-LTP and an improved performance in the Barnes maze task, suggesting a novel and potential therapeutic role in treating cognitive impairments in schizophrenia.

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来源期刊
Behavioural Brain Research
Behavioural Brain Research 医学-行为科学
CiteScore
5.60
自引率
0.00%
发文量
383
审稿时长
61 days
期刊介绍: Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.
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