Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction
Autor: | John L. Goudreau, Jessica S. Fortin, Jon S. Patterson, Erin B. Howey, Matthew J. Benskey, Harold C. Schott, Keith J. Lookingland |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Agonist
Aging medicine.medical_specialty Tyrosine 3-Monooxygenase 040301 veterinary sciences medicine.drug_class Dopamine Pituitary Diseases Pituitary pars intermedia adenoma Dopamine agonist 0403 veterinary science 03 medical and health sciences 0302 clinical medicine Internal medicine Parkinson disease animal model Pituitary pars intermedia dysfunction Animals Medicine Horses Pituitary Gland Intermediate Pergolide lcsh:Veterinary medicine General Veterinary Tyrosine hydroxylase business.industry Equine Dopaminergic Pars intermedia 04 agricultural and veterinary sciences General Medicine Endocrinology Dopamine Agonists lcsh:SF600-1100 Horse Diseases business 030217 neurology & neurosurgery Research Article medicine.drug |
Zdroj: | BMC Veterinary Research, Vol 16, Iss 1, Pp 1-8 (2020) BMC Veterinary Research |
ISSN: | 1746-6148 |
Popis: | Background Pituitary pars intermedia dysfunction (PPID) develops slowly in aged horses as degeneration of hypothalamic dopaminergic neurons leads to proliferation of pars intermedia (PI) melanotropes through hyperplasia and adenoma formation. Dopamine (DA) concentrations and tyrosine hydroxylase (TH) immunoreactivity are markedly reduced in PI tissue of PPID-affected equids and treatment with the DA receptor agonist pergolide results in notable clinical improvement. Thus, we hypothesized that pergolide treatment of PPID-affected horses would result in greater DA and TH levels in PI tissue collected from PPID-affected horses versus untreated PPID-affected horses. To test this hypothesis, pituitary glands were removed from 18 horses: four untreated PPID-affected horses, four aged and four young horses without signs of PPID, and six PPID-affected horses that had been treated with pergolide at 2 µg/kg orally once daily for 6 months. DA concentrations and TH expression levels in PI tissues were determined by high performance liquid chromatography with electrochemical detection and Western blot analyses, respectively. Results DA and TH levels were lowest in PI collected from untreated PPID-affected horses while levels in the pergolide treated horses were similar to those of aged horses without signs of PPID. Conclusions These findings provide evidence of restoration of DA and TH levels following treatment with pergolide. Equine PPID is a potential animal model of dopaminergic neurodegeneration, which could provide insight into human neurodegenerative diseases. |
Databáze: | OpenAIRE |
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