Chronic hyperhomocysteinemia provokes a memory deficit in rats in the Morris water maze task.
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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ABSTRACT: Although homocysteine (Hcy) has been widely implicated in the etiology of various physical health impairments, especially cardiovascular diseases, overwhelming evidence indicates that Hcy is also involved in the pathophysiology of schizophrenia and affective disorders. There are several mechanisms linking Hcy to biological underpinnings of psychiatric disorders. It has been found that Hcy interacts with NMDA receptors, initiates oxidative stress, induces apoptosis, triggers mitochondrial dysfunction and leads to vascular damage. Elevated Hcy levels might also contribute to cognitive impairment that is widely observed among patients with affective disorders and schizophrenia. Supplementation of vitamins B and folic acid has been proved to be effective in lowering Hcy levels. There are also studies showing that this supplementation strategy might be beneficial for schizophrenia patients with respect to alleviating negative symptoms. However, there are no studies addressing the influence of add-on therapies with folate and vitamins B on cognitive performance of patients with schizophrenia and affective disorders. In this article, we provide an overview of Hcy metabolism in psychiatric disorders focusing on cognitive correlates and indicating future directions and perspectives.Frontiers in Behavioral Neuroscience 09/2014; · 4.16 Impact Factor
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ABSTRACT: To assess the possible role of hyperhomocysteinemia (HyHcy) in delaying recovery after acute vestibular neuritis. In our retrospective study, 90 subjects were evaluated within 7 days from the beginning of an acute vertigo. All subjects had high plasma levels of homocysteine (Hcy). 46 patients were treated with homocysteine lowering therapy and betahistine for 1 month, while 44 subjects received only betahistine. Subjective symptoms were evaluated with the Dizziness Handicap Inventory (DHI) questionnaire, administered 7 days after the beginning of vertigo and again after 1 month. Moreover, postural control performed at 1 month’ control was studied with static stabilometry in a subgroup of 21 non-treated and 20 treated patients. DHI total score decreased significantly more in the subgroup of subjects treated with homocysteine lowering therapy. Moreover, posturographic data were significantly increased in non-treated compared with treated subjects. Our data support the possibility of a role of HyHcy in preventing recovery after a recent vestibular neuritis. A microvascular disorder or the neurotoxic effect of HyHcy have been considered as possible causal factors. Although not conclusive, our data are not inconsistent with the hypothesis of a poorer adaptation in patients with untreated HyHcy.Indian Journal of Otolaryngology and Head & Neck Surgery 04/2013; 65(2):146-150.
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ABSTRACT: Recent advances in the understanding of the pathophysiological mechanisms underlying Alzheimer's disease and other cognitive deficits have pointed to novel strategies for drug development. Animal models have contributed noticeably to these advances and are an indispensible part in the evaluation of therapeutics. This review is an exhaustive study of animal models of dementia and cognitive dysfunction. A thorough and critical evaluation of current rodent models of dementia, and discussion about their role in drug discovery and development have been carried out. Since dementia has multiple pathophysiological mechanisms, we have tried to provide a detailed description of various types of animal models which would depict different pathophysiological stages and causes of dementia. This review aims to better understand the prognosis, biochemical, and behavioral alterations that occur during dementia and hence facilitate drug discovery and development.Life Sciences. 01/2014;