Chronic mild hyperhomocysteinemia induces anxiety-like symptoms, aversive memory deficits and hippocampus atrophy in adult rats: New insights into physiopathological mechanisms
| Autor: | Carlos Alexandre Netto, Angela T. S. Wyse, Janaína Kolling, T.M. Dos Santos, Eduardo Farias Sanches, Cassiana Siebert |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Elevated plus maze Antioxidant Homocysteine DNA damage medicine.medical_treatment Hyperhomocysteinemia Hippocampus Hippocampal formation Anxiety Electron Transport Complex IV 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Atrophy Adenosine Triphosphate Internal medicine Avoidance Learning Medicine Cytochrome c oxidase Animals Rats Wistar Molecular Biology Memory Disorders biology business.industry General Neuroscience medicine.disease Rats Oxidative Stress 030104 developmental biology Endocrinology chemistry Chronic Disease biology.protein Neurology (clinical) business Open Field Test 030217 neurology & neurosurgery Developmental Biology DNA Damage |
| Zdroj: | Brain research. 1728 |
| ISSN: | 1872-6240 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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