Details

Autor(en) / Beteiligte

• Tang, Ting-ting
• Bi, Ming-xia
• Diao, Mei-ning
• Zhang, Xiao-yi
• Chen, Ling
• Xiao, Xue
• Jiao, Qian
• Chen, Xi
• Yan, Chun-ling
• Du, Xi-xun
• Jiang, Hong

Titel

Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson’s disease mouse model through activating GHS-R1a/D2R heterodimers

Ist Teil von

• Acta pharmacologica Sinica, 2023-08, Vol.44 (8), p.1564-1575

Ort / Verlag

Shanghai: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Growth hormone secretagogue receptor 1a (GHS-R1a) is an important G protein-coupled receptor (GPCR) that regulates a variety of functions by binding to ghrelin. It has been shown that the dimerization of GHS-R1a with other receptors also affects ingestion, energy metabolism, learning and memory. Dopamine type 2 receptor (D 2 R) is a GPCR mainly distributed in the ventral tegmental area (VTA), substantia nigra (SN), striatum and other brain regions. In this study we investigated the existence and function of GHS-R1a/D 2 R heterodimers in nigral dopaminergic neurons in Parkinson’s disease (PD) models in vitro and in vivo. By conducting immunofluorescence staining, FRET and BRET analyses, we confirmed that GHS-R1a and D 2 R could form heterodimers in PC-12 cells and in the nigral dopaminergic neurons of wild-type mice. This process was inhibited by MPP + or MPTP treatment. Application of QNP (10 μM) alone significantly increased the viability of MPP + -treated PC-12 cells, and administration of quinpirole (QNP, 1 mg/kg, i.p. once before and twice after MPTP injection) significantly alleviated motor deficits in MPTP-induced PD mice model; the beneficial effects of QNP were abolished by GHS-R1a knockdown. We revealed that the GHS-R1a/D 2 R heterodimers could increase the protein levels of tyrosine hydroxylase in the SN of MPTP-induced PD mice model through the cAMP response element binding protein (CREB) signaling pathway, ultimately promoting dopamine synthesis and release. These results demonstrate a protective role for GHS-R1a/D 2 R heterodimers in dopaminergic neurons, providing evidence for the involvement of GHS-R1a in PD pathogenesis independent of ghrelin.