在暴露于严重慢性高同型半胱氨酸血症的大鼠中，环境富集在不改变氧化还原状态的情况下逆转认知障碍和海马组织损失。

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2025-03-05 DOI:10.1016/j.bbr.2025.115522

E.F. Sanches , T.M. dos Santos , M.B. do Carmo , A.V.S. Carvalho , O.V. Ramires Junior , S.V. Sizonenko , C.A. Netto , A.T.S. Wyse

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引用次数: 0

摘要

经典同型半胱氨酸尿是一种由部分或全部胱氨酸-β合成酶（CβS）酶活性缺乏引起的遗传性疾病，最终导致大脑改变和早期动脉粥样硬化性疾病。目前，这种疾病还没有治愈的方法，治疗方法是通过饮食来降低同型半胱氨酸水平，但并非所有患者都对治疗有反应。由于其能够增加神经营养素的产生和减少大脑中的氧化应激，环境富集（EE）已被成功地用作辅助治疗中枢神经系统疾病的非药物治疗。在此，我们研究了4周富集环境对Wistar大鼠重度慢性化学诱导高同型半胱氨酸血症（HHCY）模型的影响。方法从出生第6天（P6）至第28天，对雄性和雌性动物皮下注射同型半胱氨酸（间隔12小时）。在此之后，动物连续暴露于强化环境（或标准笼子）30天。对动物进行认知和运动能力测试，并收集海马以评估氧化应激和组织学损伤。结果HHCY组动物在Morris水迷宫的参考记忆评估中出现学习障碍，在新物体识别测试中无影响。在开阔场地和水平阶梯任务中，HHCY不影响运动。HHCY大鼠海马体积减少，EE逆转。富集还能逆转空间记忆的认知障碍，改善爬梯行走的协调性和NOR测试中的识别记忆。HHCY改变了氧化还原平衡，对EE无保护作用。由于文献报道的益处和无副作用，EE可以作为改善同型半胱氨酸患者记忆和运动障碍的潜在补充疗法，但其神经保护机制有待进一步研究。

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Environmental enrichment reverses cognitive impairments and hippocampus tissue loss without altering the redox state in rats exposed to severe chronic hyperhomocysteinemia

Introduction

Classical homocystinuria is a genetic disease caused by partial or total deficiency of cystathionine-β synthase (CβS) enzyme activity, ultimately leading to brain alterations and early atherosclerotic disease. Currently, there is no cure for the disease and the treatments consist in reducing homocysteine levels through diet, however not all patients respond to therapy. Due to its ability to increase neurotrophins production and decrease oxidative stress in the brain, environmental enrichment (EE) has been used with success as an adjuvant non-pharmacological therapy for CNS disorders. Here, we investigated the effects of 4 weeks enriched environment in a severe chronic chemically-induced model of hyperhomocysteinemia (HHCY) in Wistar rats.

Methods

Animals of both sexes were subjected to homocysteine administration subcutaneously (12 h intervals) from day 6 of life (P6) to P28. After this period, animals were continuously exposed to the enriched environment (or standard cages) for 30 days. Animals were tested for cognition and locomotor abilities and hippocampi were collected for the assessment of oxidative stress and histological damage.

Results

Animals in the HHCY group showed impaired learning in the reference memory assessment in the Morris water maze with no effects in the novel objects recognition test. HHCY did not impair locomotion in the open field nor in the horizontal ladder task. HHCY rats presented decreased hippocampal volume reversed by EE. Enrichment was also able to reverse cognitive impairments in the spatial memory, improve coordination in the ladder walking and recognition memory in the NOR test. HHCY altered redox balance, with no protective effects of EE.

Conclusions

Due to its benefits and no side effects reported in literature, EE can be suggested as potential complimentary therapy to improve memory and motricity impairments in homocystinuric patients, however the mechanisms involved in this neuroprotection needs further investigation.

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.