Sex-specific trajectories of gait adaptation following partial dopaminergic lesions in a rat model of parkinsons disease

Abstract

Parkinsons disease (PD) is a neurodegenerative disorder in which gait disturbances are central to disability, yet their early manifestations remain poorly understood due to the difficulty of identifying prodromal PD in humans. Rodent models may help narrow this gap by approximating partial dopaminergic loss and enabling investigation of motor changes that precede overt symptoms. Here, we examined gait dynamics in Wistar rats following unilateral, low-dose 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra pars compacta (SNc). Animals were assessed weekly for six weeks in the horizontal ladder test, where running velocity and footfall accuracy were quantified with markerless pose estimation using DeepLabCut (DLC). Lesioned animals exhibited greater tyrosine hydroxylase (TH)-reactivity asymmetry than controls, reflected behaviorally as persistent but gradually attenuating deficits in gait precision. Errors peaked at week three and remained above baseline through week six. Velocity was preserved across groups, but sex differences emerged. Control females accelerated more steeply over time, whereas lesioned females showed attenuated gains and greater variability, while males displayed more homogeneous velocity profiles across conditions. Together, these findings indicate that partial SNc lesions reveal sex-specific trajectories of motor adaptation, a feature relevant to modeling prodromal PD. Combined with DLC-based tracking, this framework offers a practical approach for detecting early behavioral markers and supporting the identification of preclinical motor features of PD.