Serotonergic innervation of the striatum in a nonhuman primate model of Parkinson’s disease.

Serotonergic innervation of the striatum in a nonhuman primate model of Parkinson’s disease.

Publication date: Oct 04, 2019

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra and dopamine depletion in the striatum. Non-dopaminergic systems are also affected, including the serotonergic system. Enhanced striatal serotonergic innervation is a proposed compensatory mechanism for the dopaminergic deficit. Meanwhile a serotonergic deficit has been suggested as preceding the nigrostriatal dopaminergic pathology in PD. Our aim was to assess the serotonergic innervation of the striatum in a model of progressive experimental parkinsonism in macaques, from pre-symptomatic to symptomatic stages. The neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) was administered to adult macaque monkeys using a slow intoxication protocol. The intoxicated animals were classified into asymptomatic, recovered, moderate and severe parkinsonian, based on their motor behavior. The serotonergic innervation was studied by immunohistochemistry against serotonin (5-HT). In the striatum, the density of 5-HT-immunoreactive (5-HT+) axons was estimated with stereology. Images of the striatum in the immunostained sections were taken to compare the distribution patterns of the serotonergic innervation between groups. These patterns were apparently similar among the groups. Axonal density estimations showed no differences in striatal 5-HT + innervation between the intoxicated groups and the control group. Accordingly, this study fails to find significant changes in the striatal serotonergic axonal innervation in MPTP-treated monkeys, coinciding with previous biochemical findings in our model. However, it is possible that alterations in the serotonergic system in PD could be independent of axonal density changes. Consequently, the proposed role for striatal serotonin serving as a compensatory mechanism for dopaminergic denervation merits further study.

Jim’enez-S’anchez, L., Blesa, J., Del Rey, N.L., Monje, M.H., Obeso, J.A., and Cavada, C. Serotonergic innervation of the striatum in a nonhuman primate model of Parkinson’s disease. 22530. 2019 Neuropharmacology.

Concepts Keywords
Asymptomatic Dopaminergic systems
Axons Branches of biology
Biochemical Neuroscience
Control Group Brain
Dopamine Neurotransmitters
Dopaminergic Basal ganglia
Immunohistochemistry Dopamine
Intoxication TAAR1 agonists
Macaque Midbrain
Methyl Serotonin
MPTP Substantia nigra
Neurodegeneration Striatum
Neuropharmacology Serotonergic
Neurotoxin
Nigrostriatal
Parkinson
Parkinsonism
Pathology
Phenyl
Primate
Progressive
Protocol
Serotonergic
Serotonin
Striatal
Striatum
Substantia Nigra

Semantics

Type Source Name
drug DRUGBANK Serotonin
gene UNIPROT DNMT1
gene UNIPROT CD69
drug DRUGBANK Dopamine

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