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Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats

Parkinson’s disease (PD) is a progressive, degenerative disease that affects nearly 10 million people worldwide. Hallmark limb motor signs and dopamine depletion have been well studied; however, few studies evaluating early stage, prodromal biology exist. Pink1−/− rats, a rodent model of PD mitochon...

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Autores principales: Lechner, Sarah A., Welsch, Jacob M., Pahapill, Natalie K., Kaldenberg, Taylor A. R., Regenbaum, Amy, Kelm-Nelson, Cynthia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510667/
https://www.ncbi.nlm.nih.gov/pubmed/36172466
http://dx.doi.org/10.3389/fnbeh.2022.867958
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author Lechner, Sarah A.
Welsch, Jacob M.
Pahapill, Natalie K.
Kaldenberg, Taylor A. R.
Regenbaum, Amy
Kelm-Nelson, Cynthia A.
author_facet Lechner, Sarah A.
Welsch, Jacob M.
Pahapill, Natalie K.
Kaldenberg, Taylor A. R.
Regenbaum, Amy
Kelm-Nelson, Cynthia A.
author_sort Lechner, Sarah A.
collection PubMed
description Parkinson’s disease (PD) is a progressive, degenerative disease that affects nearly 10 million people worldwide. Hallmark limb motor signs and dopamine depletion have been well studied; however, few studies evaluating early stage, prodromal biology exist. Pink1−/− rats, a rodent model of PD mitochondrial dysfunction, exhibit early stage behavioral deficits, including vocal communication and anxiety, that progress during mid-to-late adulthood (6–12 months of age). Yet, the biological pathways and mechanisms that lead to prodromal dysfunction are not well understood. This study investigated the Pink1−/− rat in young adulthood (2 months of age). Mixed sex groups of Pink1−/− rats and wildtype (WT) controls were assayed for limb motor, anxiety, and vocal motor behaviors. A customized NanoString CodeSet, based on genetic work in later adulthood, was used to probe for the up regulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. In summary, the data show sex- and genotype-differences in limb motor, anxiety, and vocal motor behaviors. Specifically, female Pink1−/− rats demonstrate less anxiety-like behavior compared to male Pink1−/− rats and female rats show increased locomotor activity compared to male rats. Pink1−/− rats also demonstrate prodromal ultrasonic vocalization dysfunction across all acoustic parameters and sex differences were present for intensity (loudness) and peak frequency. These data demonstrate a difference in phenotype in the Pink1−/− model. Tuba1c transcript level was identified as a key marker negatively correlated to ultrasonic vocalization at 2 months of age. Identifying genes, such as Tuba1c, may help determine early predictors of PD pathology in the Pink1−/− rat and serve as targets for future drug therapy studies.
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spelling pubmed-95106672022-09-27 Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats Lechner, Sarah A. Welsch, Jacob M. Pahapill, Natalie K. Kaldenberg, Taylor A. R. Regenbaum, Amy Kelm-Nelson, Cynthia A. Front Behav Neurosci Behavioral Neuroscience Parkinson’s disease (PD) is a progressive, degenerative disease that affects nearly 10 million people worldwide. Hallmark limb motor signs and dopamine depletion have been well studied; however, few studies evaluating early stage, prodromal biology exist. Pink1−/− rats, a rodent model of PD mitochondrial dysfunction, exhibit early stage behavioral deficits, including vocal communication and anxiety, that progress during mid-to-late adulthood (6–12 months of age). Yet, the biological pathways and mechanisms that lead to prodromal dysfunction are not well understood. This study investigated the Pink1−/− rat in young adulthood (2 months of age). Mixed sex groups of Pink1−/− rats and wildtype (WT) controls were assayed for limb motor, anxiety, and vocal motor behaviors. A customized NanoString CodeSet, based on genetic work in later adulthood, was used to probe for the up regulation of genes involved in disease pathways and inflammation within the brainstem and vocal fold muscle. In summary, the data show sex- and genotype-differences in limb motor, anxiety, and vocal motor behaviors. Specifically, female Pink1−/− rats demonstrate less anxiety-like behavior compared to male Pink1−/− rats and female rats show increased locomotor activity compared to male rats. Pink1−/− rats also demonstrate prodromal ultrasonic vocalization dysfunction across all acoustic parameters and sex differences were present for intensity (loudness) and peak frequency. These data demonstrate a difference in phenotype in the Pink1−/− model. Tuba1c transcript level was identified as a key marker negatively correlated to ultrasonic vocalization at 2 months of age. Identifying genes, such as Tuba1c, may help determine early predictors of PD pathology in the Pink1−/− rat and serve as targets for future drug therapy studies. Frontiers Media S.A. 2022-09-12 /pmc/articles/PMC9510667/ /pubmed/36172466 http://dx.doi.org/10.3389/fnbeh.2022.867958 Text en Copyright © 2022 Lechner, Welsch, Pahapill, Kaldenberg, Regenbaum and Kelm-Nelson. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Behavioral Neuroscience
Lechner, Sarah A.
Welsch, Jacob M.
Pahapill, Natalie K.
Kaldenberg, Taylor A. R.
Regenbaum, Amy
Kelm-Nelson, Cynthia A.
Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats
title Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats
title_full Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats
title_fullStr Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats
title_full_unstemmed Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats
title_short Predictors of prodromal Parkinson’s disease in young adult Pink1−/− rats
title_sort predictors of prodromal parkinson’s disease in young adult pink1−/− rats
topic Behavioral Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9510667/
https://www.ncbi.nlm.nih.gov/pubmed/36172466
http://dx.doi.org/10.3389/fnbeh.2022.867958
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