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The central nervous system in animal models of hyperhomocysteinemia.

Abstract

Growing epidemiological evidence of associations between mildly elevated plasma homocysteine with age-related cognitive impairment, neurodegenerative and cerebrovascular disease has stimulated interest in the role of homocysteine in neurological and neuropsychiatric disorders. Homocysteine is an intermediate in the folate, vitamin B12 and B6 dependent pathways of one-carbon and sulfur amino acid metabolism. Impairments of these pathways may cause CNS dysfunction by promoting the intracellular generation of homocysteine, which is postulated to have vasotoxic and neurotoxic properties. It might also inhibit the methylation of myelin basic protein and membrane phospholipids, or disrupt biogenic amine metabolism and many other vital CNS reactions. However, it is unclear which, if any, of these putative mechanisms underlies the epidemiological associations. Genetic mouse models of hyperhomocysteinemia suggest that the primary metabolic disturbances rather than homocysteine per se may be important in determining neurological outcomes. However, severe and early developmental abnormalities in these mice limit their usefulness for understanding the relation of hyperhomocysteinemia to adult CNS disorders. Pharmacologic and dietary studies on homocysteine in rodents have reported heightened neuronal sensitivity to neurotoxic insults, neurochemical abnormalities and cerebrovascular dysfunction. Such studies are consistent with a causal relationship, but they fail to distinguish between effects that might result from a dietary imbalance and those that might be caused by homocysteine per se. Future work should be directed towards refining these models in order to distinguish between the effects of homocysteine and its determinants on neurological and behavioral outcomes that represent different CNS disorders.

Authors+Show Affiliations

Nutrition and Neurocognition Laboratory and Vitamin Metabolism and Aging Laboratory, The Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. aron.troen@tufts.edu

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

16111797

Citation

Troen, Aron M.. "The Central Nervous System in Animal Models of Hyperhomocysteinemia." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 29, no. 7, 2005, pp. 1140-51.
Troen AM. The central nervous system in animal models of hyperhomocysteinemia. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(7):1140-51.
Troen, A. M. (2005). The central nervous system in animal models of hyperhomocysteinemia. Progress in Neuro-psychopharmacology & Biological Psychiatry, 29(7), pp. 1140-51.
Troen AM. The Central Nervous System in Animal Models of Hyperhomocysteinemia. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(7):1140-51. PubMed PMID: 16111797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The central nervous system in animal models of hyperhomocysteinemia. A1 - Troen,Aron M, PY - 2005/06/17/accepted PY - 2005/8/23/pubmed PY - 2006/1/18/medline PY - 2005/8/23/entrez SP - 1140 EP - 51 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog. Neuropsychopharmacol. Biol. Psychiatry VL - 29 IS - 7 N2 - Growing epidemiological evidence of associations between mildly elevated plasma homocysteine with age-related cognitive impairment, neurodegenerative and cerebrovascular disease has stimulated interest in the role of homocysteine in neurological and neuropsychiatric disorders. Homocysteine is an intermediate in the folate, vitamin B12 and B6 dependent pathways of one-carbon and sulfur amino acid metabolism. Impairments of these pathways may cause CNS dysfunction by promoting the intracellular generation of homocysteine, which is postulated to have vasotoxic and neurotoxic properties. It might also inhibit the methylation of myelin basic protein and membrane phospholipids, or disrupt biogenic amine metabolism and many other vital CNS reactions. However, it is unclear which, if any, of these putative mechanisms underlies the epidemiological associations. Genetic mouse models of hyperhomocysteinemia suggest that the primary metabolic disturbances rather than homocysteine per se may be important in determining neurological outcomes. However, severe and early developmental abnormalities in these mice limit their usefulness for understanding the relation of hyperhomocysteinemia to adult CNS disorders. Pharmacologic and dietary studies on homocysteine in rodents have reported heightened neuronal sensitivity to neurotoxic insults, neurochemical abnormalities and cerebrovascular dysfunction. Such studies are consistent with a causal relationship, but they fail to distinguish between effects that might result from a dietary imbalance and those that might be caused by homocysteine per se. Future work should be directed towards refining these models in order to distinguish between the effects of homocysteine and its determinants on neurological and behavioral outcomes that represent different CNS disorders. SN - 0278-5846 UR - https://www.unboundmedicine.com/medline/citation/16111797/The_central_nervous_system_in_animal_models_of_hyperhomocysteinemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(05)00221-6 DB - PRIME DP - Unbound Medicine ER -