Rodent Models of Parkinson’s Disease: Beyond the Motor Symptomatology
Comparing Non-Motor Phenotypes Across Three Models
Parkinson’s disease is classically defined by its motor signs, yet non-motor symptoms such as depression, anxiety, and cognitive impairment are increasingly recognised as central to the disease and remain frequently underdiagnosed. To address this dimension, the authors set out to compare, in parallel, the motor, emotional, and cognitive profiles of three distinct rat models of Parkinson’s disease, all designed to produce dopaminergic degeneration in both hemispheres: a 6-hydroxydopamine (6-OHDA) lesion model, a paraquat (PQ) induced model, and a genetic model based on viral vector-mediated overexpression of α-synuclein. This phenotypic characterisation, drawn from an extensive battery of behavioural tests, was complemented by immunohistological quantification of the nigrostriatal lesion.
All three models reproduced the hallmark motor deficits of the disease, accompanied by a significant loss of tyrosine hydroxylase positive neurons in the substantia nigra pars compacta, although the extent of degeneration varied from roughly 20 to nearly 50 percent across models. Beyond these shared motor features, however, each model displayed a distinctive pattern of non-motor alterations. The α-synuclein model was especially characterised by reduced exploratory activity, whereas the paraquat model proved valuable for studying neuropsychiatric dysfunction, since it produced both anxiety-like and depressive-like behaviour. The 6-OHDA model, in turn, exhibited the broadest spectrum of non-motor symptoms, combining anxiety-like and depressive-like phenotypes with working memory deficits, the latter being observed only in this model.
Taken together, these findings indicate that all three models satisfy the essential requirements of a Parkinson’s disease model while offering complementary windows into its non-motor components. As such, they provide useful tools for investigating the mechanisms that underlie these symptoms and for screening candidate treatments aimed at the disease’s wider clinical picture.