In Parkinson’s disease (PD) research, 6-hydroxydopamine (6-OHDA) is one of the most widely adopted neurotoxins for modeling dopaminergic (DA) neuronal degeneration. This lesion model is generated by stereotaxic injection of 6-OHDA into specific brain regions to selectively ablate dopaminergic neurons, resulting in hallmark PD-like motor manifestations including bradykinesia, rigidity and tremor. The 6-OHDA model is extensively applied to unravel pathophysiological mechanisms underlying PD, evaluate neuroprotective interventions, and screen potential therapeutic candidates.

Among available preclinical PD models, the 6-OHDA-lesioned rodent model is regarded as the gold standard for recapitulating PD motor deficits as well as levodopa-induced dyskinesia (LID), owing to its excellent reproducibility and favorable clinical translatability. PharmaLegacy has established a 6-OHDA-induced PD rat model. Two weeks post-model establishment, we conduct open field test, cylinder test, rotarod test and gait analysis to verify model success.

PharmaLegacy adopted rasagiline as a positive control drug for pharmacodynamic evaluation based on the 6-OHDA-induced rat PD model. Drug efficacy was assessed through behavioral tests. Meanwhile, histopathological detection and molecular biochemical assays were conducted at the experimental endpoint to confirm the success of model establishment.

The AAV+PFF combined rat model represents a robust and pathophysiologically relevant preclinical Parkinson’s disease (PD) model constructed via stereotaxic intracerebral injection of adeno-associated virus (AAV) encoding α-synuclein together with pre-formed α-synuclein fibrils (PFFs). Exogenous PFFs act as seeds to trigger endogenous α-synuclein misfolding, aggregation and prion-like spreading throughout the nigrostriatal pathway, recapitulating the progressive propagation of Lewy pathology observed in clinical PD patients. Combined with sustained overexpression of α-synuclein driven by AAV vector, this dual-hit strategy synergistically accelerates pathological progression, leading to gradual loss of dopaminergic neurons in the substantia nigra pars compacta, depletion of striatal dopamine, and progressive motor dysfunction including bradykinesia, rigidity and forelimb asymmetry. Distinct from acute toxin-based PD models such as MPTP and 6-OHDA lesions that induce rapid neuronal injury, the AAV+PFF model recapitulates the slow, progressive pathological development characteristic of idiopathic PD. At PharmaLegacy, we have established this AAV+PFF-induced rat PD model, which can be comprehensively validated through longitudinal motor behavioral assessments, immunohistochemical detection of phosphorylated α-synuclein aggregates, TH-positive dopaminergic neuron quantification supporting efficacy evaluation for disease-modifying therapeutic candidates targeting α-synuclein pathology.