Quantification of brainstem norepinephrine relative to vocal impairment and anxiety in the Pink1-/- rat model of Parkinson disease

Jesse D. Hoffmeister, Cynthia A. Kelm-Nelson, Michelle R. Ciucci

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21 Scopus citations


Vocal communication impairment and anxiety are co-occurring and interacting signs of Parkinson Disease (PD) that are common, poorly understood, and under-treated. Both vocal communication and anxiety are influenced by the noradrenergic system. In light of this shared neural substrate and considering that noradrenergic dysfunction is a defining characteristic of PD, tandem investigation of vocal impairment and anxiety in PD relative to noradrenergic mechanisms is likely to yield insights into the underlying disease-specific causes of these impairments. In order to address this gap in knowledge, we assessed vocal impairment and anxiety behavior relative to brainstem noradrenergic markers in a genetic rat model of early-onset PD (Pink1-/-) and wild type controls (WT). We hypothesized that 1) brainstem noradrenergic markers would be disrupted in Pink1-/-, and 2) brainstem noradrenergic markers would be associated with vocal acoustic changes and anxiety level. Rats underwent testing of ultrasonic vocalization and anxiety (elevated plus maze) at 4, 8, and 12 months of age. At 12 months, brainstem norepinephrine markers were quantified with immunohistochemistry. Results demonstrated that vocal impairment and anxiety were increased in Pink1-/- rats, and increased anxiety was associated with greater vocal deficit in this model of PD. Further, brainstem noradrenergic markers including TH and α1 adrenoreceptor immunoreactivity in the locus coeruleus, and β1 adrenoreceptor immunoreactivity in vagal nuclei differed by genotype, and were associated with vocalization and anxiety behavior. These findings demonstrate statistically significant relationships among vocal impairment, anxiety, and brainstem norepinephrine in the Pink1-/- rat model of PD.

Original languageEnglish (US)
Article number113514
JournalBehavioural Brain Research
StatePublished - Sep 24 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the United States National Institutes of Health [NIDCD T32 DC009401; NIDCD, R01 DC014358, R01 DC018584-01A1, R21 DC016135-03].

Publisher Copyright:
© 2021 Elsevier B.V.


  • Anxiety
  • Norepinephrine
  • Parkinson disease
  • Pink1
  • Rat
  • Ultrasonic vocalization


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