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The rotenone-induced sporadic Parkinsonism model: timeline of motor and non-motor features
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  • Tyciane Nascimento,
  • Alfaete Oliveira,
  • Mônica Belém,
  • Jéssica Bezerra,
  • Marta Carmo,
  • Tiago Sampaio,
  • Armenio do Santos,
  • Rodrigo Cunha,
  • Geanne Andrade
Tyciane Nascimento
Federal University of Ceara
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Alfaete Oliveira
Federal University of Ceara
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Mônica Belém
Federal University of Ceara
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Jéssica Bezerra
Federal University of Ceara
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Marta Carmo
Federal University of Ceará
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Tiago Sampaio
Federal University of Ceara
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Armenio do Santos
Federal University of Ceará
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Rodrigo Cunha
Ctr Neuroscience Coimbra
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Geanne Andrade
Federal University of Ceará

Corresponding Author:gmatos@ufc.br

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Abstract

Warring the increasing incidence of Parkinson’s disease (PD) requires better characterized animal models, in particular of the PD prodrome. Since pesticide are well-established triggers of Parkinsonism, we now undertook a detailed characterization of the time dependent onset of behavioral and neurochemical alterations after the repeated daily i.p. administration to adult male rats of a low dose of rotenone (2.75 mg/kg) during weekdays for 21 days. The onset of motor (bradykinesia in the open field test) and coordination deficits (balance in the rotarod and rearing in the open field) occurred after 14 days of exposure to rotenone, linked to a nigrostriatal dopaminergic degeneration and increased accumulation of alpha-synuclein, which are key features of PD. Moreover, we identified several modifications pre-dating the onset of PD-like motor symptoms, encompassing gastrointestinal alterations and a modified whole-body composition together with olfactory dysfunction and memory and emotional impairments, which were typified by: i) a delayed gastric emptying of liquids (13CO2 analysis), which was evident from the third day of rotenone administration and was aggravated over subsequent days; ii) a loss of total, visceral and subcutaneous body fat and dehydration (bioimpedance spectroscopy); iii) olfactory dysfunction (discrimination test and food buried test). The characterization of this prodrome period in this robust model of PD offers a unique window of opportunity to investigate the pathophysiological mechanisms of PD onset and to devise and test novel neuroprotective strategies.
23 Aug 2024Submitted to European Journal of Neuroscience
26 Aug 2024Submission Checks Completed
26 Aug 2024Assigned to Editor
26 Aug 2024Review(s) Completed, Editorial Evaluation Pending
27 Aug 2024Reviewer(s) Assigned
17 Sep 2024Editorial Decision: Revise Major
16 Nov 20241st Revision Received
07 Dec 2024Review(s) Completed, Editorial Evaluation Pending
07 Dec 2024Submission Checks Completed
07 Dec 2024Assigned to Editor
07 Dec 2024Reviewer(s) Assigned