The expression of cannabinoid type 1 receptor and 2-arachidonoyl glycerol synthesizing/degrading enzymes is altered in basal ganglia during the active phase of levodopa-induced dyskinesia.
Neurobiology of Disease. 2018-10-01; 118: 64-75
DOI: 10.1016/j.nbd.2018.06.019
Read on PubMed
1. Neurobiol Dis. 2018 Oct;118:64-75. doi: 10.1016/j.nbd.2018.06.019. Epub 2018 Jun
21.
The expression of cannabinoid type 1 receptor and 2-arachidonoyl glycerol
synthesizing/degrading enzymes is altered in basal ganglia during the active
phase of levodopa-induced dyskinesia.
Rojo-Bustamante E(1), Abellanas MA(1), Clavero P(2), Thiolat ML(3), Li Q(4),
Luquin MR(5), Bezard E(6), Aymerich MS(7).
Author information:
(1)Universidad de Navarra, Facultad de Ciencias, Departamento de Bioquímica y
Genética, Avenida Pío XII, 31008 Pamplona, Spain; Universidad de Navarra, CIMA,
Programa de Neurociencias, Avenida Pío XII, 31008 Pamplona, Spain.
(2)Servicio de Neurología, Complejo Hospitalario de Navarra, Pamplona, Spain;
IdiSNA, Instituto de Investigación Sanitaria de Navarra, Spain.
(3)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France.
(4)Motac Neuroscience Ltd, Manchester, United Kingdom; Institute of Laboratory
Animal Sciences, China Academy of Medical Sciences, Beijing, China.
(5)Universidad de Navarra, CIMA, Programa de Neurociencias, Avenida Pío XII,
31008 Pamplona, Spain; IdiSNA, Instituto de Investigación Sanitaria de Navarra,
Spain; Clínica Universidad de Navarra, Servicio de Neurología, Avenida Pío XII,
31008 Pamplona, Spain.
(6)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France; Motac Neuroscience Ltd, Manchester, United Kingdom;
Institute of Laboratory Animal Sciences, China Academy of Medical Sciences,
Beijing, China.
(7)Universidad de Navarra, Facultad de Ciencias, Departamento de Bioquímica y
Genética, Avenida Pío XII, 31008 Pamplona, Spain; Universidad de Navarra, CIMA,
Programa de Neurociencias, Avenida Pío XII, 31008 Pamplona, Spain; IdiSNA,
Instituto de Investigación Sanitaria de Navarra, Spain. Electronic address:
.
Management of levodopa-induced dyskinesias (LID) is one of the main challenges in
the treatment of Parkinson’s disease patients. Mechanisms involved in the
appearance of these involuntary movements are not well known but modifications in
the activity of different neurotransmitter pathways seem to play an important
role. The objective of this study was to determine differences in the expression
levels of the endocannabinoid system (ECS) elements that would support a role in
LID. The basal ganglia nuclei, putamen, external segment of the globus pallidus
(GPe), internal segment of the globus pallidus (GPi), subthalamic nucleus (STN)
and substantia nigra (SN) were dissected out from cryostat sections obtained from
two groups of parkinsonian monkeys treated with levodopa to induce dyskinesias.
One group of dyskinetic animals was sacrificed under the effect of levodopa,
during the active phase of LID, and the other group 24 h after the last levodopa
dose (OFF levodopa). Biochemical analysis by real-time PCR for ECS elements was
performed. CB1 receptor expression was upregulated in the putamen, GPe and STN
during the active phase of dyskinesia and downregulated in the same nuclei and in
the SN when dyskinetic animals were OFF levodopa. Changes in the 2-arachidonoyl
glycerol (2-AG) synthesizing/degrading enzymes affecting the pallidal-subthalamic
projections in dyskinetic animals OFF levodopa would suggest that 2-AG may play a
role in LID. Anandamide (AEA) synthesizing/degrading enzymes were altered
specifically in the GPe of untreated parkinsonian monkeys, suggesting that
increased AEA levels may be a compensatory mechanism. These results indicate that
the expression of the ECS elements is influenced by alterations in dopaminergic
neurotransmission. On one hand, changes in CB1 receptor expression and in the
2-AG synthesizing/degrading enzymes suggest that they could be a therapeutic
target for the active phase of LID. On the other hand, AEA metabolism could
provide a non-dopaminergic target for symptomatic relief. However, further
research is needed to unravel the mechanism of action of the ECS and how they
could be modulated for a therapeutic purpose.
Copyright © 2018 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2018.06.019
PMID: 29936234