Transcriptome profiling of the subventricular zone and dentate gyrus in an animal model of Parkinson's disease

Abstract

Adult neurogenesis in the subventricular zone (SVZ), as well as in the subgranular zone contributes to brain maintenance and regeneration. In the adult brain, dopamine (DA) can regulate the endogenous neural stem cells within these two regions, while a DA deficit may affect neurogenesis. Notably, the factors that regulate in vivo neurogenesis in these subregions have not yet been fully characterized, particularly following DA depletion. In thi study, we performed RNA sequencing to investigate transcriptomic changes in the SVZ and dentate gyrus (DG) of mice in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This analysis identified differentially expressed genes which were involved in the regulation of transcription, immune response, extracellular region, cell junction and myelination. These genes partially displayed different temporal profiles of expression, some of which may participate in the metabolic switch related to neurogenesis. Additionally, the mitogen-activated protein kinase (MAPK) signaling pathway was shown to be been positively regulated in the SVZ, while it was negatively affected in the DG following MPTP administration. Overall, our findings indicate that exposure to MPTP may exert different effects on transcriptome profiling between the SVZ and DG.

Transcriptome profiling of five brain regions in a 6‐hydroxydopamine rat model of Parkinson’s disease

“… 23 The mitochondrial damage in the striatum of PD models has been reported previously. 24 In this study, we further found that varying degrees of mitochondrial damage were observed in all five brain regions. Whether the mechanism of mitochondrial damage in different brain regions is similar needs further investigations.…”

Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance

“…Many of the biological themes identified here with pesticides are consistent with transcriptome studies that report on transcripts and cell pathways altered with MPTP-treatments (Bao et al, 2017) and in PD patients compared to health individuals (Gollamudi et al, 2012; Glaab and Schneider, 2015; Mariani et al, 2016). Comparative pathway analysis of the brain transcriptome in PD patients compared to age-matched, non-PD subjects, revealed that gene profiles associated with mitochondria, neuron differentiation, apoptosis, ion channel, and inflammation to name but a few were major entities/processes that were altered with the disease (Glaab and Schneider, 2015).…”

Transcriptional Profiles of Cell Fate Transitions Reveal Early Drivers of Neuronal Apoptosis and Survival

“…Nr4a subfamily members are categorized as early response genes with pleiotropic physiological roles, including maintaining neuronal integrity, regulating the density and distribution of spines and synapses, suppressing apoptosis and inducing pro-survival genes [88][89][90][91]. Interestingly, a marked decrease in Nr4a1 was associated with a variety of neurological conditions, including Alzheimer's and Parkinson's diseases, schizophrenia and bipolar disorders, and various activators and modulators of this TF have been investigated as probable therapeutic drugs in neuroinflammatory and neuronal cell death models [92][93][94][95][96][97][98][99][100][101].…”