Objective: The objective of our study was to characterize the behavioral phenotype of the transgenic LRRK-2 rat in the context of PD model and to investigate the differential expression of the CDNF in the striatum and in the hippocampus.

Background: There has been considerable interest in the emergence of non-motor symptoms (NMS): changes in memory, executive function and mood, during the prodromal phase of Parkinson’s disease (PD). There is evidence to suggest that the novel neurotrophic factor: cerebral dopamine neurotrophic factors (CDNF) protects dopamine neurons in the substantia nigra (SN) in lesion PD model and regulates neuronal survival and inflammation responses. The role of the hippocampus in mediating the NMS has been largely unexplored.

Methods: We purchased 3-5 weeks old male LRRK-2 transgenic and LRRK-2 wild type rats from Taconic Farms, Ithaca, NY USA (line # 10677). All the transgenic rats were genotyped to confirm the R1441G mutation of the human LRRK-2 gene. Both the LRRK-2 transgenic rats (n=10) and LRRK-2 wild type (n=10) were allowed to acclimatize for 2 weeks prior to conducting weekly cylinder behavioral test and gross observation for 4 weeks. At the end of the 4-week period, both groups of rats were sacrificed. The dissected hippocampus and striatum were frozen at -70 C prior to assay for CDNF expression.

Results: Our results showed that both groups of LRRK-2 mutant and LRRK-2 wild type did not differ in their body weight and gross behavior. Repeated cylinder testing failed to show any significant difference in cylinder test scores at p< 0.05 level. Western blot analysis of mRNA CDNF showed that CDNF expression in the hippocampus of LRRK2 transgenic rats were 19:4 % higher than the LRRK2 wild type. The difference was statistically significant (p =0.024, two tailed t test). LRRK2 wild type rats showed a trend, albeit non-significant, towards higher mRNA CDNF level compared to the LRRK-2 transgenic group.

Conclusions: Our study demonstrates for the first time differential expression of CDNF in the hippocampus versus the striatum of LRRK-2 transgenic rats compared with the LRRK-2. implicating the emerging role of CDNF in regulating NMS phenotype in LRRK2 mutation and the hippocampus mediating NMS in the PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/differential-expression-of-cerebral-dopamine-neurotrophic-factor-cdnf-in-the-hippocampus-and-in-the-striatum-of-lrrk-2-mutant-rat-model-of-parkinsons-disease/