The Rotenone Model of Parkinson’s Disease in Studying the Mechanisms of Nigrostriatal Cell Death

Parkinson’s disease is a progressive neurodegenerative disorder of the basal ganglia for which no specific cause could be found in the majority of cases. For a long time a possible role for an environmental toxin (s) in a genetic background has been thought. Pesticides and insecticides were implicated in the increased prevalence of PD in rural areas. Rotenone is a plant derived pesticide and a complex I (NADH-quinone oxido-reductase) inhibitor. In rodents, the pesticide administered via systemic routes as well as locally into specific brain areas eg., the substantia nigra or striatum, resulted in nigrostraital cell loss, α-synuclein like cytoplasmic inclusions, and motor impairments. Rotenone induces decreased dopamine and tyrosine hydroxylase immunoreactive neurons in the striatum and substantia nigra. Changes in serotonergic, noradrenergic, and cholinergic neurotransmitters also occur. Parkinsonian like α-synuclein pathology also develops inside the spinal cord, dorsal motor nucleus of the vagus as well as in the enteric neurons in rotenone-treated rodents. Oxidative and nitrosative stress, mitochondrial dysfunction, dysfunction of the ubiquitin-proteasome pathway, protein aggregation, microtubule depolymerization, excitotoxicity, microglia activation, and neuroinflammation have been identified as important mechanisms underlying the rotenone-induced death of dopaminergic neurons. Research into the rotenone model of PD offers many possibilities for studying the pathways of cell death in PD and developing new drug therapies.