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Updated: Jun 30, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Behavioral recovery in MPTP-treated monkeys: neurochemical mechanisms studied by intrastriatal microdialysis
Sabrina Boulet1, Stéphanie Mounayar, Annie Poupard
1Institut National de la Santé et de la Recherche Médicale, Unité 836, Grenoble Institut des Neurosciences, Dynamique des Réseaux Neuronaux du Mouvement, Grenoble F-38043 Cedex 09, France.
Abstract:
Parkinson's disease (PD) patients express motor symptoms only after 60-80% striatal dopamine (DA) depletion. The presymptomatic phase of the disease may be sustained by biochemical modifications within the striatum. We used an appropriate specific 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model (Mounayar et al., 2007) to study the compensatory mechanisms operating in recovery from PD motor symptoms. We assessed the levels of DA and its metabolites (DOPAC, homovanillic acid), GABA, glutamate (Glu), serotonin (5-HT) and its metabolite (5HIAA) by repeated intracerebral microdialysis in awake animals before exposure to MPTP during full expression of the motor symptoms induced by MPTP and after recovery from these symptoms. Measurements were obtained from two functionally and anatomically different striatal areas: the associative-limbic territory and sensorimotor territory. Animals with motor symptoms displayed an extremely large decrease in levels of DA and its metabolites and an increase in Glu and GABA levels, as reported by other studies. However, we show here for the first time that serotonin levels increased in these animals. We found that increases in DA levels in the sensorimotor and/or associative-limbic territory and high levels of 5-HT and of its metabolite, 5HIAA, were associated with recovery from motor symptoms in this model. Determining whether similar changes in DA and 5-HT levels are involved in the compensatory mechanisms delaying the appearance of motor symptoms in the early stages of PD might make it possible to develop new treatment strategies for the disease.
Insights
Parkinson's disease motor symptoms appear late due to compensatory brain changes. Increased dopamine and serotonin levels correlate with symptom recovery in a monkey model, offering potential new treatment avenues.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Parkinson's disease (PD) motor symptoms manifest only after substantial striatal dopamine depletion.
- Presymptomatic PD may involve compensatory biochemical adaptations in the striatum.
Purpose of the Study:
- To investigate compensatory mechanisms underlying recovery from motor symptoms in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's disease.
- To analyze changes in neurotransmitter levels during different stages of PD symptom expression and recovery.
Main Methods:
- Repeated intracerebral microdialysis in awake MPTP-treated monkeys.
- Measurement of dopamine (DA), its metabolites (DOPAC, HVA), GABA, glutamate (Glu), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5HIAA) in associative-limbic and sensorimotor striatal territories.
- Assessment before MPTP exposure, during symptom expression, and after recovery.
Main Results:
- MPTP-induced motor symptoms were associated with decreased DA and increased Glu and GABA levels.
- For the first time, increased serotonin (5-HT) levels were observed in symptomatic animals.
- Recovery from motor symptoms correlated with increased DA in specific striatal territories and elevated 5-HT and 5HIAA levels.
Conclusions:
- Striatal dopamine and serotonin alterations are implicated in motor symptom recovery in this PD model.
- Understanding these compensatory mechanisms could lead to novel therapeutic strategies for delaying PD symptom onset.
