Article

Chronic Hyperhomocysteinemia provokes a memory defi- cit in rats in the Morris water maze task

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Behavioural Brain Research (Impact Factor: 3.39). 09/2004; 153(2):377-81. DOI: 10.1016/j.bbr.2003.12.013
Source: PubMed

ABSTRACT Homocystinuria is an inherited metabolic disease biochemically characterized by tissue accumulation of homocysteine. Affected patients present mental retardation and other neurological symptoms whose mechanisms are still obscure. In the present study, we investigated the effect of chronic hyperhomocysteinemia on rat performance in the Morris water maze task. Chronic treatment was administered from the 6th to the 28th day of life by s.c. injection of homocysteine, twice a day at 8-h intervals; control rats received the same volume of saline solution. Animals were left to recover until the 60th day of life. Morris water maze tasks were then performed, in order to verify any effect of early homocysteine administration on reference and working memory of rats. Results showed that chronic treatment with homocysteine impaired memory of the platform location and that homocysteine treated animals presented fewer crossings to the place where the platform was located in training trials when compared to saline-treated animals (controls). In the working memory task, homocysteine treated animals also needed more time to find the platform. Our findings suggest that chronic experimental hyperhomocysteinemia causes cognitive dysfunction and that might be related to the neurological complications characteristic of homocystinuric patients.

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    • "These prior studies suggest that Hcy has multiple functions in the brain; this can likely explain its links to various psychiatric disorders, including schizophrenia and affective disorders. Animals exposed to Hcy exhibit compromised brain energy metabolism (Streck et al., 2003), altered long-term potentiation, disturbances of synaptic plasticity and cognitive impairment in terms of spatial learning (Algaidi et al., 2006) and memory deficits (Streck et al., 2004). Heterozygous and homozygous Mthfr knockout mice are also characterized by neurodevelopmental retardation and altered cerebellar morphology (Chen et al., 2001). "
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    • "The group fed on 5% methionine showed an increase in time spent in the closed arms in the elevated plus maze, indicating a modification in emotional behaviour that involves structures as the amygdala and the ventral hippocampus. There is evidence that a prolonged exposition to high Hcy provoked a memory deficit in the Morris water maze task (Streck et al., 2004) and high levels of Hcy caused memory impairments (Reis et al., 2002). Moreover there is a correlation between high levels of plasma Hcy concentration and cognitive deficit assessed with the Mini-Mental State Examination (MMSE) in old depressed patients without vascular disease (Bell et al., 1992). "
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    • "Recently, it has been suggested that chronic administration of Hcy to rats affected both long-and short-term memory in the Morris water maze task (Streck et al., 2004). Additionally, in another study it was found that in AD patients, high Hcy plasma levels favored neurodegeneration (Agnati et al., 2005). "
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