Elevated γ-aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson's disease: Correlation with striatal dopamine loss

Authors

  • Dr. Stephen J. Kish PhD,

    Corresponding author
    1. Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, the Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario
    • Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada, M5T 1R8
    Search for more papers by this author
  • Ali Rajput MD,

    1. University Hospital, Saskatoon, Saskatchewan, Ontario, Canada
    Search for more papers by this author
  • Joseph Gilbert MD,

    1. Victoria Hospital, London, Ontario, Canada
    Search for more papers by this author
  • Bohdan Rozdilsky MD,

    1. University Hospital, Saskatoon, Saskatchewan, Ontario, Canada
    Search for more papers by this author
  • Li-Jan Chang MS,

    1. Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, the Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario
    Search for more papers by this author
  • Kathleen Shannak BS,

    1. Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, the Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario
    Search for more papers by this author
  • Oleh Hornykiewicz MD

    1. Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, the Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ontario
    2. University of Vienna, Vienna, Austria
    Search for more papers by this author

Abstract

We measured the concentration of γ-aminobutyric acid (GABA), glutamic acid, and o-phosphoethanolamine in autopsied brain of 9 patients who died with idiopathic Parkinson's disease and 10 control subjects. In the control striatum GABA showed an uneven rostrocaudal distribution pattern with rostral subdivisions containing about 40 to 50% higher levels. When compared with controls, GABA concentrations in Parkinson's disease striatum were generally elevated. The GABA elevation was most pronounced in the caudal subdivision of the putamen; this striatal subdivision also showed the most severe dopamine loss. We observed in the caudal putamen a significant negative correlation between the (elevated) GABA and (reduced) dopamine levels (the latter expressed as the sum of dopamine plus 3-methoxytyramine). Milder nonsignificant elevations of GABA levels were observed in intermediate and rostral putamen followed by the caudate head subdivisions. GABA levels were normal in all extrastriatal brain areas examined. Striatal glutamic acid levels were markedly elevated in 3 of the 9 patients with Parkinson's disease. We suggest that the altered GABA metabolism in the striatum, especially the putamen, is consequent to the nigrostriatal deficiency in this disorder. This secondary change in striatal GABA function is likely to contribute to the basal ganglia dysfunction produced by the striatal dopamine loss and thus may be related to certain aspects of parkinsonian symptomatology.

Ancillary