Autoradiographic labelling of metabotropic glutamate type 2/3 receptors in the hemi-parkinsonian rat brain.
J Chem Neuroanat
; 138: 102422, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38657828
ABSTRACT
L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson's disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu2/3) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu2/3 activation, we performed autoradiographic binding with [3H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [3H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30â¯% vs sham-lesioned rats, P<0.05), globus pallidus (GP, 28â¯% vs sham-lesioned rats, P<0.05; 23â¯% vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (49â¯% vs sham-lesioned rats, P<0.05; 45â¯% vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43â¯% vs mildly dyskinetic 6-OHDA-lesioned rats, P<0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30â¯% vs sham-lesioned rats; 24â¯% vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05), GP (34â¯% vs sham-lesioned rats, P<0.05; 23â¯% vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (50â¯% vs sham-lesioned rats; 44â¯% vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30â¯% vs sham-lesioned rats; 19â¯% vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [3H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all P<0.05). These results suggest that alterations in mGlu2/3 receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autoradiography
/
Brain
/
Levodopa
/
Oxidopamine
/
Receptors, Metabotropic Glutamate
Limits:
Animals
Language:
En
Journal:
J Chem Neuroanat
Journal subject:
ANATOMIA
/
NEUROLOGIA
/
QUIMICA
Year:
2024
Document type:
Article
Country of publication:
Países Bajos