Acute intranigral homocysteine administration produces stereotypic behavioral changes and striatal dopamine depletion in Sprague-Dawley rats.

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  • Additional Information
    • Source:
      Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 0045503 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-8993 (Print) Linking ISSN: 00068993 NLM ISO Abbreviation: Brain Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam Elsevier/North-Holland Biomedical Press.
    • Subject Terms:
      Corpus Striatum/*metabolism ; Dopamine/*metabolism ; Homocysteine/*pharmacology ; Stereotyped Behavior/*physiology ; Substantia Nigra/*physiology; Animals ; Body Weight/drug effects ; Corpus Striatum/drug effects ; Dopamine/deficiency ; Functional Laterality ; Homocysteine/administration & dosage ; Infusions, Parenteral ; Male ; Rats ; Rats, Sprague-Dawley ; Stereotyped Behavior/drug effects ; Substantia Nigra/drug effects
    • Abstract:
      Homocysteine has been considered a major risk factor for cardiovascular diseases, and patients with hyperhomocystinemia exhibit neurological and psychological abnormalities. Elevated level of this molecule in the blood of Parkinson's disease patients receiving long-term l-DOPA therapy prompted us to investigate whether homocysteine is neurotoxic to the nigrostriatal dopaminergic system in Sprague-Dawley rats. Animals infused unilaterally with different doses of homocysteine (0.25-1 micromol in 1 microl) intranigrally exhibited significant and dose-dependent decrease in dopamine levels in the ipsilateral striatum as assayed employing an HPLC coupled with electrochemical detector, 19 days post-infusion. While 3,4-dihydroxyphenylacetic acid level in the striatum showed a dose-dependent decrease, homovanillic acid was found to be inhibited only for the highest dose. Amphetamine administration in these animals on the 14th day caused stereotypic turning behavior ipsilateral to the side of infusion. Apomorphine challenge on the 16th day elicited stereotypic contralateral circling behavior. Neurotransmitter levels in the serotonergic perikarya or terminals were unaltered 19 days following intraraphe infusion of homocysteine, which suggested the specificity of its action to dopaminergic neurons. These results indicate nigrostriatal lesions similar to that observed following intranigral infusion of the dopaminergic neurotoxin, 6-hydroxydopamine and suggest its closeness to the parkinsonian animal model. Furthermore, these findings provide evidence for the neurotoxic nature of homocysteine to dopaminergic neurons and suggest that elevated level of this molecule in parkinsonian patients may be conducive to accelerate the progression of the disease.
    • Accession Number:
      0LVT1QZ0BA (Homocysteine)
      VTD58H1Z2X (Dopamine)
    • Publication Date:
      Date Created: 20060221 Date Completed: 20060731 Latest Revision: 20131121
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.brainres.2005.12.073
    • Accession Number:
      16487496