An update on the rotenone models of Parkinson's disease: Their ability to reproduce the features of clinical disease and model gene–environment interactions

shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson’s disease model

“…In contrast to the MPTP models employed in previous studies, rotenone exposure causes a similar degree of mitochondrial inhibition in cells throughout the brain and outside the CNS (34). Despite this widespread mitochondrial impairment, neuropathology in rotenone-exposed animals is selective and resembles PD (34,36,39,47). The model supports the idea that systemic abnormalities of mitochondrial complex I function, as reported in PD patients (15), can cause the specific pattern of neurodegeneration observed in PD.…”

“…However, recent refinements to this model -particularly the development of a reliable intraperitoneal delivery protocol using a triglyceride vehicle -have yielded more reproducible results, and rotenone has now been used in several species to model both motor and non-motor features of PD (reviewed in ref. 39). The rat rotenone model provides an appropriate setting in which to examine the role of endogenous α-synuclein in the pathogenesis of sporadic PD, because (i) the Figures 1-3).…”

How close are we to revealing the etiology of Parkinson's disease?

“…Although these and other experimental models suggested to shed light on the etiopathogenesis of PD and reproduced some key features of the disease, they did not succeed in reproducing both the pathology and progressive degenerative process in human PD [11]. However, circuitory loss and b-synchronization are shared by denervated animals and humans undergoing deep brain stimulation, and recent rotenone models combined with genetic PD models reproducing motor deficits, extranigral pathology and non-motor symptoms have shed light into the gen-environmental interactions [12].…”

Toxin-Induced Parkinson’s Disease Models

“…25 The pesticide treatment has shown to induce mitochondrial dysfunction with development of postural instability characteristic of PD. 26,27 Several studies in animals with rotenone exposure have implicated parkinsonism neurobehavioral abnormalities including locomotor defects, 28 depressive-like syndrome 29 and cognitive deficits 30 . Moreover, accumulating evidence points towards neuroprotective therapeutic intervention targeting vulnerable pathways involved in degenerative events following rotenone exposure.…”