Objective: The aim of this study was to examine the relationship between depression and Parkinson’s disease (PD) using the rat model of maternal separation (MS).

Background: There is a close relationship and interaction between depression and PD: depression is not only the non-motor feature but also the contributing factor of PD. Depression in PD is a complexity which involving in dopaminergic, noradrenergic and serotonergic systems and may be a consequence of PD pathology. Most of PD models utilized to explore the involvement in depression in PD are based on 6-OHDA-treated animals in previous studies. What is more, most of them are simply observational investigations of the changes in behavioral and histochemical test. Thus, they can’t fully explain the underlying molecular mechanism between them.

Method: We used sucrose preference test, buried food pellet test and colorectal distension test to evaluate depressive behaviors of the experimental rats. Open field test and automated gait analysis were used to examine motor dysfunction in 60 weeks after MS. 5-HT1AR (Hippocampus) and DAT (Striatum) were examined by PET-CT with 18F-Mefway and 18F-FPCIT. Transcriptome sequencing was used to determine the differentially expressed genes (DEGs) in striatum at 60-week old.

Results: At different time points during the study period, the non-motor function and motor function of MS rats had different damage levels. Compared with control group, the 5-HT1AR (Hippocampus) and DAT (Striatum) of MS rats decreased at 36-week old. A total of 1204 DEGs were determined in striatum at 60-week old, including 155 up-regulated genes and 1049 downregulated genes. Subsequently, we performed KEGG analysis to reveal potential signaling pathway and GO enrichment analysis to reveal potential biological process, molecular function and cellular component involved in these DEGs. Functional analysis showed that among all pathways Dopaminergic synapse was surprisingly found. In addition, locomotion was involved in the top-twenty terms of biological process and neuromuscular process controlling balance was also found among all terms of biological process.

Conclusion: The different vulnerability of non-motor function and motor function after MS was based on age. Many biological processes involving in both depression and PD were consequently changed after MS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-life-stress-offers-a-window-into-the-relationship-between-depression-and-parkinsons-disease-a-60-week-study-after-maternal-separation-in-rats/