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Chronic mild hyperhomocysteinemia induces anxiety-like symptoms, aversive memory deficits and hippocampus atrophy in adult rats: New insights into physiopathological mechanisms.
- Source :
-
Brain research [Brain Res] 2020 Feb 01; Vol. 1728, pp. 146592. Date of Electronic Publication: 2019 Dec 06. - Publication Year :
- 2020
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Abstract
- In the last decade, increased homocysteine levels have been implicated as a risk factor for neurodegenerative and psychiatric disorders. We have developed an experimental model of chronic mild hyperhomocysteinemia (HHcy) in order to observe metabolic impairments in the brain of adult rodents. Besides its known effects on brain metabolism, the present study sought to investigate whether chronic mild HHcy could induce learning/memory impairments associated with biochemical and histological damage to the hippocampus. Adult male Wistar rats received daily subcutaneous injections of homocysteine (0.03 μmol/g of body weight) twice a day, from the 30th to the 60th day of life or saline solution (Controls). After injections, anxiety-like and memory tests were performed. Following behavioral analyses, brains were sliced and hippocampal volumes assessed and homogenized for redox state assessment, antioxidant activity, mitochondrial functioning (chain respiratory enzymes and ATP levels) and DNA damage analyses. Behavioral analyses showed that chronic mild HHcy may induce anxiety-like behavior and impair long-term aversive memory (24 h) that was evaluated by inhibitory avoidance task. Mild HHcy decreased locomotor and/or exploratory activities in elevated plus maze test and caused hippocampal atrophy. Decrease in cytochrome c oxidase, DNA damage and redox state changes were also observed in hippocampus of adult rats subjected to mild HHcy. Our findings show that chronic mild HHcy alters biochemical and histological parameters in the hippocampus, leading to behavioral impairments. These findings might be considered in future studies aiming to search for alternative strategies for treating the behavioral impairments in patients with mild elevations in homocysteine levels.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Adenosine Triphosphate metabolism
Animals
Anxiety pathology
Atrophy etiology
Atrophy pathology
Avoidance Learning
Chronic Disease
DNA Damage physiology
Electron Transport Complex IV metabolism
Hippocampus physiopathology
Homocysteine blood
Hyperhomocysteinemia chemically induced
Male
Memory Disorders physiopathology
Open Field Test
Oxidative Stress physiology
Rats
Rats, Wistar
Anxiety etiology
Hippocampus pathology
Hyperhomocysteinemia complications
Memory Disorders etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1728
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 31816318
- Full Text :
- https://doi.org/10.1016/j.brainres.2019.146592