{"title":"异丙酚对mptp诱导的帕金森病大鼠模型认知和海马n -甲基- d -天冬氨酸亚基表达的影响","authors":"Ping Zhu, Yongyan Zhang, Hua Xu, Yu Ren","doi":"10.3389/fnbeh.2025.1607421","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) is associated with higher risk of cognitive impairment. Until now, little is known about the effect of anesthetics on cognitive function in PD patients. The imbalance of hippocampal N-methyl-D-aspartate (NMDA) receptors NR2A/NR2B subunit ratio is reported to be associated with memory dysfunction in PD rats. The current study investigated the effects of propofol on the cognitive function and hippocampal NR2A/NR2B ratio in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model.</p><p><strong>Methods: </strong>MPTP was stereotaxically injected into the substantia nigra pars compacta of male Wistar rats. Next day (day 2), the rats in the chronic intervention groups were injected daily with either propofol (80 mg/kg/day, i.p.) or fat emulsion for 7 days (day 2-8). The rats in the acute intervention groups received propofol or fat emulsion only on day 8. Then, all the rats underwent an open field test and an inhibitory avoidance (IA) test. At last, the rats were killed for histological analysis and hippocampal NR2A and NR2B proteins and mRNA level quantification.</p><p><strong>Results: </strong>Neither acute nor chronic treatment with propofol can significantly change the impairment of locomotor activity and dopaminergic denervation of the striatum in MPTP-lesioned rats. MPTP lesioning caused IA memory impairment, which was aggravated by chronic treatment with propofol. Furthermore, chronic treatment with propofol also aggravated the imbalance of hippocampal NR2A/NR2B ratio in MPTP-lesioned rats.</p><p><strong>Discussion: </strong>The current findings indicate that chronic propofol treatment exacerbated MPTP-induced inhibitory avoidance (IA) memory impairment and aggravated the imbalance of hippocampal NR2A/NR2B ratio in MPTP-lesioned rats. Our current data demonstrate a correlation, not direct causation, between NR2A/NR2B dysregulation and cognitive impairment. Future studies should probe whether this imbalance is a driver or consequence of synaptic dysfunction.</p>","PeriodicalId":12368,"journal":{"name":"Frontiers in Behavioral Neuroscience","volume":"19 ","pages":"1607421"},"PeriodicalIF":2.6000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171286/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effects of propofol on the cognition and hippocampal N-methyl-D-aspartate subunits expression in an MPTP-induced Parkinson's disease rat model.\",\"authors\":\"Ping Zhu, Yongyan Zhang, Hua Xu, Yu Ren\",\"doi\":\"10.3389/fnbeh.2025.1607421\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Parkinson's disease (PD) is associated with higher risk of cognitive impairment. Until now, little is known about the effect of anesthetics on cognitive function in PD patients. The imbalance of hippocampal N-methyl-D-aspartate (NMDA) receptors NR2A/NR2B subunit ratio is reported to be associated with memory dysfunction in PD rats. The current study investigated the effects of propofol on the cognitive function and hippocampal NR2A/NR2B ratio in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model.</p><p><strong>Methods: </strong>MPTP was stereotaxically injected into the substantia nigra pars compacta of male Wistar rats. Next day (day 2), the rats in the chronic intervention groups were injected daily with either propofol (80 mg/kg/day, i.p.) or fat emulsion for 7 days (day 2-8). The rats in the acute intervention groups received propofol or fat emulsion only on day 8. Then, all the rats underwent an open field test and an inhibitory avoidance (IA) test. At last, the rats were killed for histological analysis and hippocampal NR2A and NR2B proteins and mRNA level quantification.</p><p><strong>Results: </strong>Neither acute nor chronic treatment with propofol can significantly change the impairment of locomotor activity and dopaminergic denervation of the striatum in MPTP-lesioned rats. MPTP lesioning caused IA memory impairment, which was aggravated by chronic treatment with propofol. Furthermore, chronic treatment with propofol also aggravated the imbalance of hippocampal NR2A/NR2B ratio in MPTP-lesioned rats.</p><p><strong>Discussion: </strong>The current findings indicate that chronic propofol treatment exacerbated MPTP-induced inhibitory avoidance (IA) memory impairment and aggravated the imbalance of hippocampal NR2A/NR2B ratio in MPTP-lesioned rats. Our current data demonstrate a correlation, not direct causation, between NR2A/NR2B dysregulation and cognitive impairment. 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引用次数: 0
摘要
简介：帕金森病（PD）与认知障碍的高风险相关。到目前为止，人们对麻醉药对PD患者认知功能的影响知之甚少。海马n -甲基- d -天冬氨酸（NMDA）受体NR2A/NR2B亚基比失衡与PD大鼠记忆功能障碍有关。本研究研究了异丙酚对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD大鼠模型认知功能和海马NR2A/NR2B比值的影响。方法：将MPTP立体定向注入雄性Wistar大鼠黑质致密部。第二天（第2天），慢性干预组大鼠每天注射异丙酚（80 mg/kg/天，i.p.）或脂肪乳，连续7 天（第2-8天）。急性干预组大鼠仅在第8天给予异丙酚或脂肪乳。然后，所有大鼠进行了开放场试验和抑制回避（IA）试验。最后处死大鼠进行组织学分析和海马NR2A、NR2B蛋白及mRNA水平定量。结果：急性和慢性异丙酚治疗均不能显著改变mptp损伤大鼠的运动活性和纹状体多巴胺能失神经支配的损害。MPTP损伤引起IA记忆损伤，慢性异丙酚治疗加重了这种损伤。此外，异丙酚慢性治疗也加重了mptp损伤大鼠海马NR2A/NR2B比例失衡。讨论：目前的研究结果表明，慢性异丙酚治疗加重了mptp诱导的抑郁性回避（IA）记忆障碍，加重了mptp损伤大鼠海马NR2A/NR2B比例失衡。我们目前的数据表明，NR2A/NR2B失调与认知障碍之间存在相关性，而不是直接因果关系。未来的研究应该探讨这种不平衡是突触功能障碍的驱动因素还是结果。
Effects of propofol on the cognition and hippocampal N-methyl-D-aspartate subunits expression in an MPTP-induced Parkinson's disease rat model.
Introduction: Parkinson's disease (PD) is associated with higher risk of cognitive impairment. Until now, little is known about the effect of anesthetics on cognitive function in PD patients. The imbalance of hippocampal N-methyl-D-aspartate (NMDA) receptors NR2A/NR2B subunit ratio is reported to be associated with memory dysfunction in PD rats. The current study investigated the effects of propofol on the cognitive function and hippocampal NR2A/NR2B ratio in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model.
Methods: MPTP was stereotaxically injected into the substantia nigra pars compacta of male Wistar rats. Next day (day 2), the rats in the chronic intervention groups were injected daily with either propofol (80 mg/kg/day, i.p.) or fat emulsion for 7 days (day 2-8). The rats in the acute intervention groups received propofol or fat emulsion only on day 8. Then, all the rats underwent an open field test and an inhibitory avoidance (IA) test. At last, the rats were killed for histological analysis and hippocampal NR2A and NR2B proteins and mRNA level quantification.
Results: Neither acute nor chronic treatment with propofol can significantly change the impairment of locomotor activity and dopaminergic denervation of the striatum in MPTP-lesioned rats. MPTP lesioning caused IA memory impairment, which was aggravated by chronic treatment with propofol. Furthermore, chronic treatment with propofol also aggravated the imbalance of hippocampal NR2A/NR2B ratio in MPTP-lesioned rats.
Discussion: The current findings indicate that chronic propofol treatment exacerbated MPTP-induced inhibitory avoidance (IA) memory impairment and aggravated the imbalance of hippocampal NR2A/NR2B ratio in MPTP-lesioned rats. Our current data demonstrate a correlation, not direct causation, between NR2A/NR2B dysregulation and cognitive impairment. Future studies should probe whether this imbalance is a driver or consequence of synaptic dysfunction.
期刊介绍：
Frontiers in Behavioral Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the neural mechanisms underlying behavior. Field Chief Editor Nuno Sousa at the Instituto de Pesquisa em Ciências da Vida e da Saúde (ICVS) is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
This journal publishes major insights into the neural mechanisms of animal and human behavior, and welcomes articles studying the interplay between behavior and its neurobiological basis at all levels: from molecular biology and genetics, to morphological, biochemical, neurochemical, electrophysiological, neuroendocrine, pharmacological, and neuroimaging studies.
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