Dopamine D1 + D3 receptor density may correlate with parkinson disease clinical features

Abstract

ObjectiveDopamine D2‐like receptors – mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R) – are believed to be greatly involved in the pathology of Parkinson disease (PD) progression. However, these receptors have not been precisely examined in PD patients. Our aim was to quantitatively calculate the exact densities of dopamine D1 receptors (D1R), D2R, and D3R in control, Alzheimer disease (AD), and Lewy body disease (LBD) patients (including PD, Dementia with Lewy bodies, and Parkinson disease dementia); and analyze the relationship between dopamine receptors and clinical PD manifestations.MethodsWe analyzed the densities of D1R, D2R, and D3R in the striatum and substantia nigra (SN) using a novel quantitative autoradiography procedure previously developed by our group. We also examined the expression of D2R and D3R mRNA in the striatum by in situ hybridization.ResultsThe results showed that although no differences of striatal D1R were found among all groups; D2R was significantly decreased in the striatum of PD patients when compared with control and AD patients. Some clinical manifestations: age of onset, PD stage, dopamine responsiveness, and survival time after onset; showed a better correlation with striatal D1R + D3R densities combined compared to D1R or D3R alone.InterpretationThere is a possibility that we may infer the results in diagnosis, treatment, and prognosis of PD by detecting D1R + D3R as opposed to using dopamine D1 or D3 receptors alone. This is especially true for elderly patients with low D2R expression as is common in this disease.

Immunomodulatory Effects of Dopamine in Inflammatory Diseases

“…Striatal D1-D3R heteromers are closely correlated with age of onset, PD stage, dopamine responsiveness, and survival time (129). Besides, the expression of D3R induced by long-term L-DOPA treatment aggravates D1R oversensitivity and is correlated with the severity of LID, via activating D1R/Shp-2/ Erk1/2 pathway (130).…”

Bioactive lipids and their metabolism: New therapeutic opportunities for Parkinson's disease

“…Alternatively, dopamine receptors provide another potential target for pharmacotherapy. Among these, dopamine D2‐like receptors belonging to the category of G protein‐coupled receptors, mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R), are believed to be greatly involved in the pathology of PD progression (Yang et al, 2021). Nowadays, partial D2R agonists have been used in the clinical interventions of PD, including an ergoline derivative (apomorphine) that have already rarely been applied in clinic due to its irreversible side effects, as well as non‐ergoline derivatives (pramipexole, ropinirole and rotigotine) that have effective antiparkinsonian properties and reduce the symptoms of PD or the levodopa‐induced dyskinesia in PD.…”

Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulated in Exercise in a Mouse Model of Parkinson’s Disease

“…Impaired higher cortical function was found in patients with PD and FMRI showed enhanced connectivity in the M1 region of the motor cortex after an 8-week exercise treatment in patients ( Messa et al, 2019 ). Moreover, decreased dopamine receptors D1 and D3 in the cerebellum was found in patients with PD ( Yang et al, 2021 ). RRHO and WGCNA have been previously applied to generate insight into other diseases.…”