PET studies: in vivo monitoring of group I metabotropic glutamate receptors in Parkinson’s disease rat

Aim: Parkinson’s disease (PD) is known as one of neurodegenerative disorders caused by aggregation of amyloid-like protein alpha-synuclein (α-syn). The group I metabotropic glutamate receptors (mGluR1 and mGluR5) play important roles in excitatory neurotransmission upon the central nerves system (CNS). To investigate relationship between group I metabotropic glutamate receptors and degeneration of dopaminergic neurons, we determined the change of mGluR1 and mGluR5 expressions during degeneration of dopaminergic neurons using PET imaging with three radioligands.Methods: Four to sixteen months old female human α-syn transgenic (R6/2) and noncarrier rats were used in this study. Respective locomotion and rearing scores of rats were evaluated by open-field test. PET studies on the rats were performed using [11C]ITDM (radiochemical purity: >99%; specific activity: 37–120 GBq/µmol) for mGluR1, (E)-[11C]ABP688 (>99%; 91–170 GBq/µmol) for mGluR5 or [18F]FEPE2I (>99%; 37–55 GBq/µmol) for dopamine transporter (DAT) by a small-animal PET scanner (Inveon). Acquired PET data were analysed with reference tissue models by PMOD software. The respective reference tissues were located on the pons for mGluR1 and cerebellum for mGluR5 and DAT.Results: Pathology of PD was found in R6/2 rats at eight to ten months old. In the PET studies, compared to noncarrier rats, striatal binding potential (BPND) of [11C]ITDM showed temporal increase during four to six months old but decreased after six months. Meanwhile, striatal BPND of (E)-[11C]ABP688 showed increase during six to ten months old in R6/2 rats. The BPND of [18F]FEPE2I, a biomarker of dopaminergic neurons, started to decrease during eight to ten months old in R6/2 rats, which corresponded with progression of PD pathology.Conclusion: Our study indicates that up-regulation of mGluR1 in early phase of PD and subsequent up-regulation of mGluR5 may be involved in degeneration of dopaminergic neuron. Therefore, monitoring of group I metabotropic glutamate receptors would be a useful tool for furtherunderstanding of pathological mechanism of PD.EANM Congress 201