The rotenone-induced sporadic Parkinsonism model: timeline of motor and
non-motor features
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.