Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1 −/− rats
Abstract Background Parkinson disease (PD) is the fastest growing neurodegenerative disease. The molecular pathology of PD in the prodromal phase is poorly understood; as such, there are no specific prognostic or diagnostic tests. A validated Pink1 genetic knockout rat was used to model early-onset...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Neuroscience |
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| Online Access: | https://doi.org/10.1186/s12868-024-00857-0 |
| _version_ | 1827328497304993792 |
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| author | Sarah A. Lechner David G. S. Barnett Stephen C. Gammie Cynthia A. Kelm-Nelson |
| author_facet | Sarah A. Lechner David G. S. Barnett Stephen C. Gammie Cynthia A. Kelm-Nelson |
| author_sort | Sarah A. Lechner |
| collection | DOAJ |
| description | Abstract Background Parkinson disease (PD) is the fastest growing neurodegenerative disease. The molecular pathology of PD in the prodromal phase is poorly understood; as such, there are no specific prognostic or diagnostic tests. A validated Pink1 genetic knockout rat was used to model early-onset and progressive PD. Male Pink1 −/− rats exhibit progressive declines in ultrasonic vocalizations as well as hindlimb and forelimb motor deficits by mid-to-late adulthood. Previous RNA-sequencing work identified upregulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. The purpose of this study was to identify gene pathways within the whole blood of young Pink1 −/− rats (3 months of age) and to link gene expression to early acoustical changes. To accomplish this, limb motor testing (open field and cylinder tests) and ultrasonic vocalization data were collected, immediately followed by the collection of whole blood and RNA extraction. Illumina® Total RNA-Seq TruSeq platform was used to profile differential expression of genes. Statistically significant genes were identified and Weighted Gene Co-expression Network Analysis was used to construct co-expression networks and modules from the whole blood gene expression dataset as well as the open field, cylinder, and USV acoustical dataset. ENRICHR was used to identify the top up-regulated biological pathways. Results The data suggest that inflammation and interferon signaling upregulation in the whole blood is present during early PD. We also identified genes involved in the dysregulation of ribosomal protein and RNA processing gene expression as well as prion protein gene expression. Conclusions These data identified several potential blood biomarkers and pathways that may be linked to anxiety and vocalization acoustic parameters and are key candidates for future drug-repurposing work and comparison to human datasets. |
| first_indexed | 2024-03-07T15:17:48Z |
| format | Article |
| id | doaj.art-2b5e408ac7a6493c981a632b7130fa19 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-03-07T15:17:48Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-2b5e408ac7a6493c981a632b7130fa192024-03-05T17:47:44ZengBMCBMC Neuroscience1471-22022024-03-0125111510.1186/s12868-024-00857-0Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1 −/− ratsSarah A. Lechner0David G. S. Barnett1Stephen C. Gammie2Cynthia A. Kelm-Nelson3Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Medical Sciences Center, University of Wisconsin–MadisonDepartment of Surgery, Division of Otolaryngology-Head and Neck Surgery, Medical Sciences Center, University of Wisconsin–MadisonDepartment of Integrative Biology, University of WisconsinDepartment of Surgery, Division of Otolaryngology-Head and Neck Surgery, Medical Sciences Center, University of Wisconsin–MadisonAbstract Background Parkinson disease (PD) is the fastest growing neurodegenerative disease. The molecular pathology of PD in the prodromal phase is poorly understood; as such, there are no specific prognostic or diagnostic tests. A validated Pink1 genetic knockout rat was used to model early-onset and progressive PD. Male Pink1 −/− rats exhibit progressive declines in ultrasonic vocalizations as well as hindlimb and forelimb motor deficits by mid-to-late adulthood. Previous RNA-sequencing work identified upregulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. The purpose of this study was to identify gene pathways within the whole blood of young Pink1 −/− rats (3 months of age) and to link gene expression to early acoustical changes. To accomplish this, limb motor testing (open field and cylinder tests) and ultrasonic vocalization data were collected, immediately followed by the collection of whole blood and RNA extraction. Illumina® Total RNA-Seq TruSeq platform was used to profile differential expression of genes. Statistically significant genes were identified and Weighted Gene Co-expression Network Analysis was used to construct co-expression networks and modules from the whole blood gene expression dataset as well as the open field, cylinder, and USV acoustical dataset. ENRICHR was used to identify the top up-regulated biological pathways. Results The data suggest that inflammation and interferon signaling upregulation in the whole blood is present during early PD. We also identified genes involved in the dysregulation of ribosomal protein and RNA processing gene expression as well as prion protein gene expression. Conclusions These data identified several potential blood biomarkers and pathways that may be linked to anxiety and vocalization acoustic parameters and are key candidates for future drug-repurposing work and comparison to human datasets.https://doi.org/10.1186/s12868-024-00857-0Parkinson diseasePink1−/−RNA-sequencingRatWhole blood |
| spellingShingle | Sarah A. Lechner David G. S. Barnett Stephen C. Gammie Cynthia A. Kelm-Nelson Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1 −/− rats BMC Neuroscience Parkinson disease Pink1−/− RNA-sequencing Rat Whole blood |
| title | Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1 −/− rats |
| title_full | Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1 −/− rats |
| title_fullStr | Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1 −/− rats |
| title_full_unstemmed | Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1 −/− rats |
| title_short | Prodromal Parkinson disease signs are predicted by a whole-blood inflammatory transcriptional signature in young Pink1 −/− rats |
| title_sort | prodromal parkinson disease signs are predicted by a whole blood inflammatory transcriptional signature in young pink1 rats |
| topic | Parkinson disease Pink1−/− RNA-sequencing Rat Whole blood |
| url | https://doi.org/10.1186/s12868-024-00857-0 |
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