Rodent Models of Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and the presence of intracellular α-synuclein aggregates known as Lewy bodies. While PD is traditionally associated with motor symptoms such as bradykinesia, rigidity, tremors, and postural instability, a growing body of evidence highlights a wide array of non-motor symptoms, including depression, cognitive decline, and autonomic dysfunction that often precede motor manifestations by years. Despite advances in our understanding of PD, the precise etiopathology remains elusive, and no curative or disease-modifying therapies are currently available. As such, animal models play an indispensable role in PD research by helping to elucidate the complex pathophysiological mechanisms and offering platforms for therapeutic testing. This chapter provides a comprehensive overview of rodent models of PD, emphasizing both neurotoxin-induced and genetic approaches. Neurotoxin-based models, including those using reserpine, haloperidol, 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and rotenone, are widely utilized due to their ability to replicate dopaminergic neuronal loss and motor dysfunction. These models are instrumental for studying disease pathology and assessing symptomatic treatments. Genetic models, developed through the manipulation of PD-associated genes such as α-synuclein, DJ-1, PINK1, and LRRK2, allow for the exploration of familial PD mechanisms and progressive neurodegeneration in a controlled manner. Each model offers distinct advantages and limitations, and selecting the most suitable one depends on the specific research objective, whether it involves understanding molecular mechanisms, studying disease progression, or evaluating potential therapeutic strategies. By integrating insights from both toxin-induced and genetic models, researchers can better capture the multifaceted nature of PD and advance the search for effective therapies.