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对MPTP暴露雌性大鼠抑郁样行为的影响:细胞凋亡与α-突触核蛋白调节

Effects on the Depressive-like Behavior of MPTP-Exposed Female Rats: Apoptosis and α-Synuclein Modulation.

作者信息

Savall Anne Suély Pinto, De Mello Jhuly Dorneles, Fidelis Eduarda Monteiro, Bortolotto Vandreza Cardoso, Dahleh Mustafa Munir Mustafa, Guerra Gustavo Petri, Prigol Marina, Puntel Robson, Boldori Jean Ramos, Denardin Cristiane Casagrande, Sampaio Tuane Bazanella, Pinton Simone

机构信息

Research Group on Biochemistry and Toxicology in Eukaryotes, Federal University of Pampa-Campus Uruguaiana, Uruguaiana 97500-970, RS, Brazil.

Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules (LaftamBio), Federal University of Pampa-Campus Itaqui, Itaqui 97650-000, RS, Brazil.

出版信息

Brain Sci. 2025 Jan 3;15(1):41. doi: 10.3390/brainsci15010041.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder marked by motor deficits and non-motor symptoms, such as depression, which are associated with dopaminergic loss and α-synuclein aggregation in the brain. This study investigated the neuroprotective effects of a hydroalcoholic extract of the purple fruit of (PFEU) on motor ability and depressive-like behaviors in a PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in female Wistar rats. Rats received intranasal administration of MPTP or vehicle, followed by 14 days of oral administration of PFEU (300 or 2000 mg/kg, administered once daily) or vehicle. Depressive-like behavior was assessed using the splash and forced swimming tests, while motor ability was evaluated using the rotarod and open field tests. On day 15, hippocampal tissue was collected for immunoreactivity analysis. MPTP treatment induced depressive-like behavior, which was significantly reversed by PFEU, as evidenced by increased grooming and decreased immobility. No motor coordination or locomotion deficits were observed. Furthermore, PFEU treatment prevented the MPTP-induced increase in hippocampal α-synuclein, p-p53, and Bax while restoring Bcl-2 levels, suggesting neuroprotective effects through the modulation of apoptotic pathways and α-synuclein. These findings support PFEU's potential as a neuroprotective agent for MPTP-induced depressive-like behavior in female rats, highlighting its molecular mechanisms.

摘要

帕金森病(PD)是一种神经退行性疾病,其特征为运动功能障碍和非运动症状,如抑郁症,这些症状与大脑中多巴胺能神经元丧失和α-突触核蛋白聚集有关。本研究调查了紫果水醇提取物(PFEU)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的雌性Wistar大鼠帕金森病模型的运动能力和抑郁样行为的神经保护作用。大鼠经鼻内给予MPTP或赋形剂,随后连续14天口服PFEU(300或2000 mg/kg,每日一次)或赋形剂。使用溅水试验和强迫游泳试验评估抑郁样行为,使用转棒试验和旷场试验评估运动能力。在第15天,收集海马组织进行免疫反应性分析。MPTP处理诱导了抑郁样行为,PFEU可显著逆转该行为,表现为梳理行为增加和不动时间减少。未观察到运动协调或运动缺陷。此外,PFEU处理可防止MPTP诱导的海马α-突触核蛋白、p-p53和Bax增加,同时恢复Bcl-2水平,表明其通过调节凋亡途径和α-突触核蛋白发挥神经保护作用。这些发现支持PFEU作为一种神经保护剂对MPTP诱导的雌性大鼠抑郁样行为的潜在作用,并突出了其分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fee/11764100/31ae7a0a5960/brainsci-15-00041-g001.jpg

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