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Alterations of a Nigro‐Vagal Pathway in a Rodent Model of Parkinson's Disease
Author(s) -
Hampton Jessica,
Anselmi Laura,
Travagli R. Alberto
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.869.10
Subject(s) - substantia nigra , medicine , vagus nerve , pars compacta , endocrinology , anesthesia , dopaminergic , dopamine , stimulation
Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor impairment resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Prodromal to the classic motor symptoms, a majority of PD patients experience gastrointestinal (GI) dysfunction such as reduced gastric motility, dysphagia, and severe constipation. Upper GI tract functions are modulated by vago‐vagal reflexes originating in the dorsal vagal complex (DVC) of the brainstem. We have recently described a novel nigro‐vagal connection that, when activated in response to NMDA microinjections in the SNpc, increases gastric tone and motility via vagal brainstem pathways. The aim of the present study was to elucidate the functions of the nigro‐vagal connection in a rodent model of Parkinson's disease. Male Sprague Dawley rats received 3 once‐weekly intraperitoneal injections of 10mg/kg paraquat (10P, n=4) or saline (control, n=3). Motor function was assessed following the second and third injections, as well as 2 weeks after the end of treatment. Two‐four weeks after the end of treatment, rats were anesthetized and gastric motility and tone were recorded via strain gauges surgically affixed to the anterior corpus and antrum of the stomach. Modulation of gastric activity via the nigro‐vagal pathway and by direct vagal pathways was assessed upon microinjection of NMDA (5.25 nmoles/210nl) in the SNpc and thyrotropin‐releasing‐hormone (TRH; 1‐3‐10pmol/60nl) in the DVC, respectively. Rats were then perfused‐fixed and the stomachs were collected for analysis of the neurochemical phenotype of SNpc, DVC and myenteric plexus neurons. Rats treated with paraquat showed a significant motor impairment compared to controls (stepping test, p<0.05). Moreover immunohistochemistry results showed presence of misfolded α‐synuclein (a hallmark for PD) in DVC and SNpc, confirming the validity of the PD model used in the present study. The gastric motility response to NMDA microinjection in the SNpc was decreased (p<0.05), while gastric responses to microinjections of TRH in the DVC were not significantly reduced. NOS immunoreactivity in myenteric plexus neurons was similar across all groups, suggesting that changes in gastric responses were likely due to alterations in the nigro‐vagal pathway, rather than alterations in neurochemical phenotype of the gastric myenteric neurons. These data indicate that the nigro‐vagal pathway is compromised in an established rodent model of Parkinson's disease, offering further insight into the etiology and neuropathophysiology of Parkinson's disease. Support or Funding Information NIH DK 55530