{"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. 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":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Behavioral Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnbeh.2025.1607421","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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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