Metabolic effects of nigrostriatal denervation in basal ganglia.

In the past, functional changes in the circuitry of the basal ganglia that occur in Parkinson's disease were primarily analyzed with electrophysiological and 2-deoxyglucose measurements. The increased activity of the subthalamic nucleus (STN) observed has been attributed to a reduction in inhibition mediated by the external segment of the globus pallidus (GPe), secondary to the loss of dopaminergic-neuron influence on D2-receptor-bearing striato-pallidal neurons. More recently, in situ hybridization studies of cytochrome oxidase subunit I have confirmed the overactivity of the STN in the parkinsonian state. In addition, this technique has provided evidence that the change in STN activity is owing not only to decreased inhibition from the GPe but to hyperactivity of excitatory inputs from the parafascicular nucleus of the thalamus and the pedunculopontine nucleus in the brainstem.

Neurotoxic effect of prenatal exposure to MPTP on the dopaminergic systems of the marmoset brain.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was incidentally administered to pregnant marmosets during the whole gestational period, except for the last 15 days before term. The infant monkeys were killed 5 months after birth, and dopamine and its metabolites were measured in the striatum and the nucleus accumbens. Prenatal exposure to MPTP produced a marked dopamine depletion in these brain regions of the offspring, showing that MPTP is able to cross the placental barrier in primates.

Ultradian and circadian body temperature and activity rhythms in chronic MPTP treated monkeys.

The body temperature and locomotor activity rhythms of seven 1-Methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgous monkeys were registered over a week on two separate occasions over an interval of 2 months. Motor disability was absent in two animals and present in five: it was mild in one, moderate in two and severe in two. Both temperature and motor activity were recorded every minute using a radio telemetry system. Analysis of circadian rhythms revealed less robustness of the 24-hour circadian components of body temperature and locomotor activity with increasing motor impairment, and a fragmentation of the body temperature rhythm into 8 hour-period components. Both total activity and daytime activity correlated inversely with the degree of motor impairment. On the contrary, the monkeys did not show differences in night time activity. The proportions of variance accounted for by the body temperature and locomotor activity of 24 h + 12 h + 8 h components were correlated. Also, the average levels at which the circadian rhythm varies between body temperature and locomotor activity were correlated. The results were almost identical in the two 1-week recording sessions. The present study confirms individual differences in the vulnerability to MPTP of the nigrostriatal system of monkeys, suggesting that if a cumulative dose does not provoke stable motor alterations, this cumulative dose will not produce circadian body temperature and locomotor activity rhythm alterations either. Similarly, if a dose is able to produce motor impairment, this dose will also be able to produce circadian rhythm alterations.