Experimental laboratory study
Glutamatergic compensatory mechanisms in experimental parkinsonism

https://doi.org/10.1016/S0278-5846(98)00030-XGet rights and content

Abstract

  • 1.

    1. Injection cannulae allowing access to the SNc were implanted bilaterally in four monkeys. Once animals had recovered from the operation, daily low-dose treatment with MPTP was started.

  • 2.

    2. Group I comprised two monkeys under treatment with MPTP, but still asymptomatic. Group II comprised two monkeys treated with MPTP and presenting clinical symptoms.

  • 3.

    3. Both groups received daily intracranial injections of kynurenic acid in order to block the glutamatergic afferents to the SNc.

  • 4.

    4. In the first group of asymptomatic monkeys, kynurenic acid induced parkinsonian motor abnormalities. In the second group of symptomatic monkeys, it increased the severity of clinical signs.

  • 5.

    5. Glutamatergic inputs to the SNc would therefore appear to be implicated in compensatory phenomena at different stages of experimental parkinsonism.

References (45)

  • A. Parent et al.

    Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop

    Brain Res. Rev.

    (1995)
  • A. Parent et al.

    Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry

    Brain Res. Rev.

    (1995)
  • M.J. Zigmond et al.

    Compensations after lesions of central dopaminergic neurons: some clinical and basic implications

    Trends Neurosci.

    (1990)
  • Y. Agid

    Parkinson's disease: Pathophysiology

    Lancet

    (1991)
  • P. Anglade et al.

    Is dopaminergic cell death accompanied by concomitant nerve pasticity?

  • A. Benazzouz et al.

    Alleviation of experimental hemiparkmsonism by high frequency stimulation of the subthalamic nucleus in primates: a comparison with L-Dopa treatment

    Mov. Disord.

    (1996)
  • A. Benazzouz et al.

    Reversal of rigidity and improvement in motor performance by subthalamic high frequency stimulation in MPTP-treated monkeys

    Eur. J. Neurosci.

    (1993)
  • H. Bergman et al.

    The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism

    J. Neurophysiol.

    (1994)
  • E. Bezard et al.

    Blockage of SNc glutamatergic inputs, a new base for presymtomatic diagnosis in Parkinson's disease?

    Soc. Neurosci. Abstr.

    (1996)
  • E. Bezard et al.

    Presymptomatic revelation of experimental parkinsonism

    Neuroreport

    (1997)
  • E. Bezard et al.

    Kinetics of nigral degeneration in a chronic model of MPTP-treated mice

    Neurosci. Lett

    (1997)
  • W. Birkmayer et al.

    Dopaminergic supersensitivity in parkinsonism

  • Cited by (11)

    • Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys

      2012, Neurobiology of Disease
      Citation Excerpt :

      These mechanisms could occur through the intermediary of the striatum itself as well as through extrastriatal structures (Bezard et al., 2001) as DA neurons innervate all the basal ganglia structures. Compensation could be caused by non-dopaminergic systems, such as GABAergic (Schroeder and Schneider, 2002), glutamatergic (Bezard et al., 1998) and serotoninergic systems (Gaspar et al., 1993). To go further in the understanding of these mechanisms, we developed in a previous study a monkey model of PD with progressive MPTP intoxication (Mounayar et al., 2007).

    • Towards a dynamic approach of experimental parkinsonism

      1998, Progress in Neuro-Psychopharmacology and Biological Psychiatry
    View all citing articles on Scopus
    View full text