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下丘脑外侧区深部脑刺激对老年大鼠记忆衰退及海马神经丝蛋白表达功能障碍的影响

Effect of deep brain stimulation for lateral hypothalamic area on memory decline and hippocampal neurofilaments expression dysfunctions in aged rats.

作者信息

Saad Somaya, Abouelnaga Ahmed F, Abass Marwa, Obydah Walaa, Kiwan Nedaa A, Ammar Omar Abd-Alhakem, Abulseoud Osama A, Hussein Abdelaziz M

机构信息

Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Department of Animal Behavior and Management, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.

出版信息

Neuroreport. 2025 May 14;36(8):402-411. doi: 10.1097/WNR.0000000000002162. Epub 2025 Apr 11.

Abstract

OBJECTIVE

Studying the effect of deep brain stimulation (DBS) in the lateral hypothalamic area (LHA) in young and aging rats regarding memory changes, hippocampal neuronal dystrophy, and neurofilament expression.

METHODS

Thirty-six male Sprague-Dawley rats were divided into two main groups: adult young ( n  = 18, 8 weeks old) and aged ( n  = 18, 24 months old). Each main group was further subdivided into three equal subgroups ( n  = 6) including control, sham, and DBS. DBS of LHA was conducted using high-frequency electric currents (130 Hz) for 1.5 h with 5-min breaks every 30 min for five consecutive days. Assessment of working memory was done using passive avoidance test (PAT). Then, the brain was dissected and hippocampal neuronal dystrophic damage was assessed as well as immunohistochemical examination of neurofilaments (NF68, NF200) expression.

RESULTS

Aging rats had progressive hippocampal neuronal degeneration and downregulation of heavy and light chain neurofilaments, that was associated with progressive decline in working memory. Nevertheless, activation of DBS in the LHA enhanced memory function as it increased latency to entry in PAT ( P  < 0.001) compared to old normal and sham groups. Dystrophic damage score significantly decreased with DBS ( P  < 0.001) in the hippocampal CA1, CA3, and dentate gyrus regions. Moreover, DBS upregulated hippocampal NF68, NF200 expression ( P  < 0.001) in both young and old rats. We also found a significant positive correlation between working memory and NFs expression and a negative correlation between dystrophic damage score and NFs expression.

CONCLUSIONS

DBS in the LHA may have a neuroprotective effect in aging rats as it enhanced the working memory and decreased hippocampal neuronal dystrophy. This protective effect may be caused by the upregulation of neurofilaments.

摘要

目的

研究在年轻和老龄大鼠的下丘脑外侧区(LHA)进行深部脑刺激(DBS)对记忆变化、海马神经元营养不良及神经丝表达的影响。

方法

36只雄性Sprague-Dawley大鼠分为两个主要组:成年年轻组(n = 18,8周龄)和老龄组(n = 18,24月龄)。每个主要组再进一步分为三个相等的亚组(n = 6),包括对照组、假手术组和DBS组。使用高频电流(130Hz)对LHA进行DBS,持续1.5小时,每30分钟休息5分钟,连续5天。使用被动回避试验(PAT)评估工作记忆。然后,解剖大脑,评估海马神经元营养不良性损伤,并对神经丝(NF68、NF200)表达进行免疫组化检查。

结果

老龄大鼠出现进行性海马神经元变性以及重链和轻链神经丝下调,这与工作记忆的逐渐下降有关。然而,与老龄正常组和假手术组相比,LHA中DBS的激活增强了记忆功能,因为它增加了进入PAT的潜伏期(P < 0.001)。DBS使海马CA1、CA3和齿状回区域的营养不良性损伤评分显著降低(P < 0.001)。此外,DBS上调了年轻和老龄大鼠海马中NF68、NF200的表达(P < 0.001)。我们还发现工作记忆与神经丝表达之间存在显著正相关,营养不良性损伤评分与神经丝表达之间存在负相关。

结论

LHA中的DBS可能对老龄大鼠具有神经保护作用,因为它增强了工作记忆并减少了海马神经元营养不良。这种保护作用可能是由神经丝上调引起的。

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