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6-Hydroxydopamine injections into the nigrostriatal pathway attenuate striatal malonate and 3-nitropropionic acid lesions.
Exp Neurol. 1998 Dec; 154(2):637-44.EN

Abstract

The mitochondrial inhibitors malonate and 3-nitropropionic (3NP) acid are potent neurotoxins in vivo. Administration of these compounds results in neuronal loss similar to that seen in Huntington's disease. Although the mechanism of cell death produced by these compounds likely involves activation of N-methyl-D-aspartate receptors, it remains unclear why the striatum demonstrates regional susceptibility to the toxicity of these and other mitochondrial poisons. We hypothesized that dopamine, a weak neurotoxin that occurs in high concentrations in the striatum, may contribute to the neuronal damage caused by mitochondrial inhibition. We investigated whether depletion of striatal dopamine using the catecholaminergic toxin 6-hydroxydopamine would attenuate lesions induced by mitochondrial inhibition. We found that dopamine depletion reduced significantly the extent of histological damage in the striatum elicited by both intraparenchymal injections of 0.8 micromol malonate and 20 mg/kg systemic administration of 3NP. These data suggest that dopamine or one of its metabolites may contribute to mitochondrial toxin-induced cell death.

Authors+Show Affiliations

Department of Neurology, University of Kentucky Medical Center, Lexington, Kentucky, 40536-0284, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9878198

Citation

Maragos, W F., et al. "6-Hydroxydopamine Injections Into the Nigrostriatal Pathway Attenuate Striatal Malonate and 3-nitropropionic Acid Lesions." Experimental Neurology, vol. 154, no. 2, 1998, pp. 637-44.
Maragos WF, Jakel RJ, Pang Z, et al. 6-Hydroxydopamine injections into the nigrostriatal pathway attenuate striatal malonate and 3-nitropropionic acid lesions. Exp Neurol. 1998;154(2):637-44.
Maragos, W. F., Jakel, R. J., Pang, Z., & Geddes, J. W. (1998). 6-Hydroxydopamine injections into the nigrostriatal pathway attenuate striatal malonate and 3-nitropropionic acid lesions. Experimental Neurology, 154(2), 637-44.
Maragos WF, et al. 6-Hydroxydopamine Injections Into the Nigrostriatal Pathway Attenuate Striatal Malonate and 3-nitropropionic Acid Lesions. Exp Neurol. 1998;154(2):637-44. PubMed PMID: 9878198.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 6-Hydroxydopamine injections into the nigrostriatal pathway attenuate striatal malonate and 3-nitropropionic acid lesions. AU - Maragos,W F, AU - Jakel,R J, AU - Pang,Z, AU - Geddes,J W, PY - 1999/1/8/pubmed PY - 1999/1/8/medline PY - 1999/1/8/entrez SP - 637 EP - 44 JF - Experimental neurology JO - Exp Neurol VL - 154 IS - 2 N2 - The mitochondrial inhibitors malonate and 3-nitropropionic (3NP) acid are potent neurotoxins in vivo. Administration of these compounds results in neuronal loss similar to that seen in Huntington's disease. Although the mechanism of cell death produced by these compounds likely involves activation of N-methyl-D-aspartate receptors, it remains unclear why the striatum demonstrates regional susceptibility to the toxicity of these and other mitochondrial poisons. We hypothesized that dopamine, a weak neurotoxin that occurs in high concentrations in the striatum, may contribute to the neuronal damage caused by mitochondrial inhibition. We investigated whether depletion of striatal dopamine using the catecholaminergic toxin 6-hydroxydopamine would attenuate lesions induced by mitochondrial inhibition. We found that dopamine depletion reduced significantly the extent of histological damage in the striatum elicited by both intraparenchymal injections of 0.8 micromol malonate and 20 mg/kg systemic administration of 3NP. These data suggest that dopamine or one of its metabolites may contribute to mitochondrial toxin-induced cell death. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/9878198/6_Hydroxydopamine_injections_into_the_nigrostriatal_pathway_attenuate_striatal_malonate_and_3_nitropropionic_acid_lesions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(98)96918-7 DB - PRIME DP - Unbound Medicine ER -