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雌激素激素治疗后围绝经期雌性大鼠认知和功能行为的分析。

Analysis of the cognitive and functional behavior of female rats in the periestropause after hormone therapy with estrogen.

作者信息

Esperança Thainá Daguane, Stringhetta-Villar Beatriz Procópio, Cavalcante Débora Prazias, Douradinho Luana Galante, Fiais Gabriela Alice, Pereira Rafael, Chaves-Neto Antonio Hernandes, Lima Fernanda Barbosa, Dornelles Rita Cássia Menegati

机构信息

Multicentric Graduate Program in Physiological Sciences- SBFis/UNESP, São Paulo State University, Araçatuba, São Paulo, Brazil; Aging Biology Research Group, Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.

Multicentric Graduate Program in Physiological Sciences- SBFis/UNESP, São Paulo State University, Araçatuba, São Paulo, Brazil.

出版信息

Behav Brain Res. 2024 Mar 28;462:114866. doi: 10.1016/j.bbr.2024.114866. Epub 2024 Jan 15.

Abstract

Perimenopause is a critical period, with severe cycle irregularity and lower estrogen secretion altering redox state biomarkers, leading to behavioral changes. The estrogen hormonal therapy (EHT) being commonly used to alleviate climacteric effects. Therefore, the aim of this study was to analyze anxiolytic profile, recognition memory (short and long term), ambulation, redox status, cell synaptic activity in locus coeruleus and hippocampus of Wistar rats in the periestropause after EHT. Forty rats participated in the study; 20 were treated with corn oil (group 21Mo/Veh; corn oil/0.2 mL/sc; 2x/week) and 20 were submitted to EHT (group 21Mo/E2; 17β-estradiol/15 μg/Kg/sc; 2x/week) for 120 days. Open field, elevated plus maze, object recognition (RO), and footprint tests were performed immediately before and at the end of the treatment period. From the decapitated brains, isolated hippocampus were destined for biochemical analysis, in turn, perfused brains were destined for histological analysis. The 21Mo/E2 group had a significantly greater total time in the central region and a significantly greater number of entries into the open arms compared to the 21Mo/Veh group, as in crossing, rearing and grooming behaviors, evidencing an anxiolytic profile. In the RO test, the 21Mo/Veh group decreased long-term memory, and the 21Mo/E2 group maintained the same index as at 17 months of age, in addition to a better balance of the hippocampal redox state, prevention of neuronal cell loss and better gait. Based on the results, it appears that exogenous E2 supplementation during periestropause may help preserve neurological functions and potentially prevent neuropsychological and neurodegenerative disorders.

摘要

围绝经期是一个关键时期,严重的月经周期不规律和雌激素分泌减少会改变氧化还原状态生物标志物,导致行为变化。雌激素激素疗法(EHT)常用于缓解更年期症状。因此,本研究的目的是分析EHT后围绝经期Wistar大鼠的抗焦虑特征、识别记忆(短期和长期)、行走、氧化还原状态、蓝斑和海马体中的细胞突触活动。40只大鼠参与了该研究;20只接受玉米油治疗(21Mo/Veh组;玉米油/0.2 mL/皮下注射;每周2次),20只接受EHT(21Mo/E2组;17β-雌二醇/15 μg/Kg/皮下注射;每周2次),持续120天。在治疗期开始前和结束时立即进行旷场试验、高架十字迷宫试验、物体识别(RO)试验和足迹试验。从断头的大脑中,分离出的海马体用于生化分析,而灌注的大脑用于组织学分析。与21Mo/Veh组相比,21Mo/E2组在中央区域的总时间显著更长,进入开放臂的次数显著更多,在穿越、直立和梳理行为方面也是如此,表明具有抗焦虑特征。在RO试验中,21Mo/Veh组的长期记忆下降,而21Mo/E2组保持了与17月龄时相同的指标,此外海马体氧化还原状态的平衡更好,预防了神经元细胞丢失,步态也更好。基于这些结果,似乎围绝经期补充外源性E2可能有助于维持神经功能,并可能预防神经心理和神经退行性疾病。

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