Brain Serotonin Transporter Binding In a Minipig Model of Parkinson's Disease

Research output: Contribution to conferencePosterResearch

Objectives:
Some of the debilitating non-motor aspects of Parkinson’s disease (PD) are related to the serotonin system1. To investigate the involvement of the brain serotonergic system in a PD animal model, we measured the in vivo binding of [11C]-DASB to the serotonin transporter (SERT) as a marker of serotonergic neurons. In this study, we use the in vivo capabilities of PET imaging to study serotonin neurotransmission in a minipig model of PD induced by the intracerebroventricular injection of lactacystin, an inhibitor of the ubiquitin proteasome system.


Methods:
Five female Göttingen minipigs were implanted in the cisterna magna with a catheter connected to a subcutaneous titanium injection port under sterile conditions. Six-eight weeks after recovery from the catheter implant, and after injections of sterile saline alone to verify patency, minipigs were scanned at baseline with [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (11C-DASB), a label of SERT availability. Four pigs then received eight weekly injections of lactacystin dissolved in sterile saline, and one pig received saline alone, directly into the CSF through the access port. They were scanned with DASB again after a cumulative dose of 200μg lactacystin. PET data were registered to an average minipig MRI atlas and processed using PMOD software. The binding potential (BPND) of DASB was obtained with the Logan graphical analysis and cerebellum activity as a region of non-displaceable binding.

Results:
Lactacystin administration induced behavioural symptoms including weakness of hindlimbs and decreased motor activity. SERT binding potential was decreased by 35-40% in striatal brain regions and by 20% in thalamic regions compared to the baseline scans.

Conclusions:
Our imaging data suggests a loss of brain serotonergic innervation in response to protein aggregation. The decreased striatal binding of DASB observed in this minipig model of PD is to some extend consistent with previous studies done in PD patients2. The proteasome inhibition model may therefore be useful in the investigation of non-motor deficits in PD and LDOPA-induced dyskinesia.
Original languageEnglish
Publication year30 Jun 2015
Publication statusPublished - 30 Jun 2015
EventBrain & Brain PET 2015: XXVIIth International Symposium on Cerebral Blood Flow, Metabolism and Function and the XIIth International Conference on Quantification of Brain Function with PET - Vancouver Convention Centre, Vancouver, Canada
Duration: 27 Jul 201530 Sep 2015

Conference

ConferenceBrain & Brain PET 2015
LocationVancouver Convention Centre
CountryCanada
CityVancouver
Period27/07/201530/09/2015

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