Tyciane Nascimento

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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.