Early-life stress induces prodromal features of Parkinsonian with aging in rats

Early-life stress (ELS) can cause long-term effects on human health, ranging from adolescence to adulthood, and even to gerontic. Although clinical retrospective data suggest that ELS may be related to senile neurodegenerative diseases such as Parkinson’s disease (PD), there are few prospective investigations to explore its real contribution to PD. Here, we investigated the behavioral, histochemistical, neuromorphological and transcriptional changes induced by maternal separation (MS), an ELS model. Without neurotoxin, MS rats showed behavioral alterations in olfaction, locomotion and gait characters after depression compared with control rats. Based on neuroimaging and histochemistry, although we found that the dopaminergic system in striatum was impaired after MS, the decrease of striatal dopamine level was ~33%. Consistently, tyrosine hydroxylase immune-staining positive neurons of MS rats in the substantia nigra showed deficit by about 20% in cell counting. Furthermore, using transcriptome sequencing, we discovered many differentially expressed genes (DEGs) of MS rats in striatum significantly enriched in the pathway of dopaminergic synapse, and the biological process of locomotion and neuromuscular process controlling balance. Encouragingly, some representative DEGs relating to PD were singled out. These results suggest that ELS-depression rats potentially mimic some key features of prodromal stage of PD during natural senescence. In conclusion, our findings provide some novel insights into the future pathogenesis and therapeutic studies for PD related to depression.