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

IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES
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

Abstract

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
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.
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