Project description:Early-onset pathology and reliable disease biomarkers for diagnostics are poorly understood for progressive degenerative disorders such as Parkinson disease (PD). PD is the second most common age-related degenerative disorder. The Pink1-/- rat is a mitochondrial dysfunction model of prodromal PD. In this study, we used RNA sequencing to examine gene expression within whole blood samples of young and old Pink1-/- rats as compared to age-matched wildtype controls.
Project description:Parkinson’s disease (PD) is a progressive degenerative disease. Behaviorally, voice deficits including soft monotone speech appear early and are present in 90% of individuals with PD. However, the pathology, at the level of the nucleus ambiguus, mediating voice deficits is unknown. RNA sequencing was used to examine nucleus ambiguus differential gene expression in male Pink1-/- rats compared to age-matched wildtype controls.
Project description:Loss of function in the PTEN-induced kinase 1 gene (Pink1) causes an early-onset, autosomal recessive form of PD. The translational Pink1-/- rat shows cranial sensorimotor deficits including: declines in ultrasonic vocalization, negative impacts on social vocal function, and alterations to thyroarytenoid muscle structure. The aim of this study was to identify differentially expressed genes using RNA-sequencing and bioinformatic analysis of the thyroarytenoid muscle of male Pink1-/- rats compared to wildtype controls. To construct gene co-expression networks and gene modules, a WGCNA was used to identify biological networks of interest including where Pink1 was a central node with interconnecting genes. Data are congruent with previous findings demonstrating changes to thyroarytenoid muscle structure. These data are consistent with the hypothesis that differences in peripheral biology may influence the early pathogenesis of vocalizations at the level of the thyroarytenoid muscle.
Project description:Parkinson’s disease (PD) is a degenerative disease with prodromal pathology hypothesized to manifest in lower brainstem regions as well as within peripheral systems. Behaviorally, vocal deficits including soft monotone speech appear early and are present in 90% of PD patients. However, the pathology mediating voice deficits is unknown. The Pink1-/- rat is a mitochondrial dysfunction model of prodromal PD. In this study, we used RNA sequencing to examine gene expression within the vocal fold muscle of female Pink1-/- rats as compared to age-matched wildtype controls. Comparative gene expression profiling analysis using data obtained from the RNA-sequencing between the two genotypes (Pink1-/- and WT).
Project description:Background: Parkinson’s disease (PD) is a progressive, degenerative disease with early-stage pathology hypothesized to manifest in brainstem regions. Vocal deficits, including soft monotone speech, result in significant clinical and quality of life issues and are present in 90% of PD patients; yet, the underlying pathology mediating these significant voice deficits is unknown. The Pink1-/- rat is a valid model of early-onset PD that presents with analogous vocal communication deficits (e.g. reduced loudness). Previous work shows abnormal α-synuclein protein aggregation in the periaqueductal gray (PAG), a brain region critical and necessary to the modulation of mammalian vocal behavior. In this study, we used high-throughput RNA sequencing to examine gene expression within the PAG of both male and female Pink1-/- rats as compared to age-matched wildtype controls. We used a bioinformatic approach to (1) test the hypothesis that loss of Pink1 in the PAG will influence expression of genes that interact with Pink1, (2) highlight other key genes that relate to Mendelian PD, and (3) catalog molecular targets important for the production of rat vocalizations. Results: Knockout of the Pink1 gene resulted in differentially expressed genes for both male and female rats. Pathway analysis highlighted several significant metabolic pathways. Weighted gene co-expression network analysis (WGCNA) was used to identify gene nodes and their interactions in (A) males, (B) females, and (C) combined-sexes datasets. For each analysis, within the module containing the Pink1 gene, Pink1 itself was the central node with the highest number of interactions with other genes including solute carriers, glutamate metabotropic receptors, and genes associated with protein localization. Strong connections between Pink1 and Krt2 and Hfe were found in both males and female datasets. In females a number of modules were significantly correlated with vocalization traits. Of interest, gene enrichment of the key vocal Cyan module in females showed a significant number of neuromodulatory genes including Nts, Slc6a4, Slc10a4, Ndnf, and Gpr160, that may be responsible for the modulation of rat vocalizations. The top biological pathways within the female Cyan vocal module included the regulation of membrane depolarization, indolalkylamine metabolic process, and monoamine transport. Conclusions: Overall, this work supports the premise that gene expression changes in the PAG may contribute to the vocal behavioral and deficits observed in this PD rat model. Additionally, this dataset identifies genes that represent new therapeutic targets for PD voice disorders.
Project description:This study investigates the proteomic alterations in striatal synaptic mitochondria isolated from 3-month-old wild-type and Pink1 KO rats using the SWATH-MS strategy. This dataset consists of 32 raw MS files, comprising 8 DIA (SWATH) and 24 DDA runs on a TripleTOF 5600 (SCIEX). Our findings revealed synaptic mitochondrial proteomic changes due to loss of Pink1.