title: The rotenone-induced rat model of Parkinson's disease: behavioral and electrophysiological findings.
abstract: Exposure to rotenone leads to parkinsonian features, such as loss of dopaminergic neurons in the substantia nigra and motor impairment, however, the validity of this model has recently been questioned. In rodent and monkey models of Parkinson's disease (PD) abnormal neuronal activity in the basal ganglia motor loop has been described, with hyperactivity of the subthalamic nucleus (STN) similar to that found in PD. The present study aims at providing new and more specific evidence for the validity of the rotenone rat model of PD by examining whether neuronal activity in the STN is altered. Male Sprague Dawley rats were treated with rotenone injections (2.5mg/kg bodyweight intraperitoneally) for 60 days. Behavioral analysis showed an impairment in the rotarod and hanging wire test in the rotenone group (p<0.05), accompanied by a decline in tyrosine hydroxylase immunoreactive neurons in the nigro-striatal region (p<0.001). Thereafter, single unit (SU) activities and local field potentials were recorded in the STN in urethane anesthetized rats. The SU analysis revealed a higher neuronal discharge rate (p<0.001), more bursts per minute (p=0.006) and a higher oscillatory activity (p=0.008) in the STN of rotenone treated rats. Spectral analysis showed an increase of relative beta power in the STN as well as in the motor cortex. We found electrophysiological key features of PD pathology and pathophysiology in the STN of rotenone treated rats. Therefore, the rotenone-induced rat model of PD deserves further attention since it covers more aspects than dopamine depletion and implies the reproducibility of PD specific features.
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Hannover, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: von Wrangel
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Hannover, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schwabe
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Hannover, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: John
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Hannover, Germany.
authors.forename: Joachim K
authors.initials: JK
authors.lastname: Krauss
authors.affiliation: Department of Neurosurgery, Hannover Medical School, Hannover, Germany. Electronic address: alam.mesbah@mh-hannover.de.
authors.forename: Mesbah
authors.initials: M
authors.lastname: Alam
mesh_terms: D000818:Animals; D001611:Beta Rhythm / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009044:Motor Cortex / Q000187:drug effects / Q000503:physiopathology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D012402:Rotenone / Q000633:toxicity*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase
keywords: Local field potentials; Mitochondrial complex I; Parkinson's disease; Rotenone; Single unit activity; Subthalamic nucleus