In Vivo Parkinson's Disease Models & Pharmacology Services

The unilateral 6-hydroxydopamine (6-OHDA) rat model is a well-established toxin-based model of Parkinson's disease. Stereotaxic injection of 6-OHDA into the right striatum and substantia nigra induces selective degeneration of the nigrostriatal dopaminergic pathway, resulting in motor impairment, reduced tyrosine hydroxylase (TH) expression, and neuroinflammatory activation. Following model establishment, Madopar is orally administered once daily for 20 consecutive days, followed by comprehensive behavioral testing (OFT, Grip Strength, Rotarod) and brain histopathological analysis.

Experimental flow design

Behavioral characterization

The 6-OHDA-induced Parkinson's disease rat model successfully recapitulated key motor deficits, including reduced locomotor activity, decreased grip strength, and impaired motor coordination. These abnormalities were effectively ameliorated by Madopar, confirming the model's responsiveness to dopaminergic replacement therapy.

Pathological & IF analysis

TH IF in the Striatum: Reduced TH signal in the model group, indicating dopaminergic terminal damage; TH expression was partially restored following oral Madopar treatment.

TH IF in the Substantia Nigra: Loss of dopaminergic neurons in the model group; increased TH signal with Madopar, indicating partial neuroprotection.

Neuroinflammation evaluation

Inflammatory factors in CSF: 6-OHDA induced significant elevation of inflammatory factors (IL-1β, IL-6, TNF-α) in cerebrospinal fluid (CSF) by ELISA; oral Madopar attenuated this inflammatory response.

Iba1 IF in the Striatum: Increased Iba1 signals in the model group indicated microglial activation; Madopar reduced microglial activation in the striatum.

Iba1 IF in the Substantia Nigra: Consistent microglial activation in the model group observed in the substantia nigra; Madopar similarly attenuated microglial changes.

Repeated escalating intraperitoneal administration of MPTP in C57BL/6 mice induces progressive nigrostriatal dopaminergic dysfunction. MPTP is converted to MPP⁺, which preferentially enters dopaminergic neurons and impairs mitochondrial complex I, leading to oxidative stress and dopaminergic neurodegeneration. To validate assay sensitivity, two mechanistically distinct reference compounds were incorporated: Selegiline and Madopar. Following model establishment and reference compound treatment, animals underwent behavioral testing (OFT, Grip Strength, and Rotarod) and subsequent brain histopathological analysis.

Experimental flow design

Pharmacological validation with Selegiline

Behavioral characterization

Repeated MPTP administration induced clear motor impairment, including reduced locomotor activity, decreased grip strength, and impaired motor coordination. Selegiline significantly attenuated these behavioral deficits; however, performance was not fully restored to control levels.

Pathological & IF analysis

TH IF in the Striatum: Reduced TH expression in the model group, indicating dopaminergic terminal damage; Selegiline partially preserved TH signals.

TH IF in the Substantia Nigra: Loss of dopaminergic neurons in the model group; TH signals were significantly but incompletely restored following Selegiline treatment.

Pharmacological validation with Madopar

Behavioral characterization

Subacute MPTP treatment induced significant motor deficits, including reduced grip strength and impaired rotarod performance; these abnormalities were effectively ameliorated by Madopar.

Pathological & IF analysis

TH IF in the Substantia Nigra: MPTP-associated TH loss was observed in the model group; Madopar significantly ameliorated TH loss in the substantia nigra, supporting the responsiveness of this model to dopaminergic replacement therapy.

Stereotaxic delivery of AAV9-CMV-α-synuclein into the substantia nigra induces sustained α-synuclein overexpression and progressive nigrostriatal dopaminergic dysfunction. This model captures key features of synucleinopathy, including motor impairment, dopaminergic neuronal injury, and pathogenic α-synuclein accumulation. Following model establishment, UCB0599 is intraperitoneally (i.p.) administered once daily for 48 consecutive days, followed by comprehensive behavioral testing (OFT, Grip Strength, Rotarod) and brain histopathological analysis.

Experimental flow design

Behavioral characterization

The AAV9-CMV-α-synuclein-induced Parkinson's disease mouse model successfully recapitulated key motor deficits, including reduced locomotor activity, decreased grip strength, and impaired motor coordination. These abnormalities were effectively ameliorated by UCB0599, confirming the model's responsiveness to α-synuclein-targeted therapy.

Pathological & IF analysis

TH IF in the Striatum: Reduced TH signal in the model group, indicating dopaminergic terminal damage; TH fluorescence was increased following UCB0599 treatment.

TH IF in the Substantia Nigra: Loss of dopaminergic neurons in the model group; TH signal was restored with UCB0599, indicating neuroprotection.

pSer129 IF in the Substantia Nigra: Marked accumulation of pathological pSer129-α-synuclein in the model group; UCB0599 significantly reduced pSer129-α-synuclein signals, supporting its potential to attenuate α-synuclein-associated nigrostriatal pathology.

Intrastriatal injection of α-synuclein preformed fibrils (PFFs) triggers progressive α-synuclein pathology and nigrostriatal dysfunction, recapitulating the prion-like seeding and spreading of pathological α-syn observed in Parkinson's disease. Motor performance was evaluated 112 days after PFF administration using Open Field, Grip Strength, and Rotarod tests — a timepoint capturing the late-onset, progressive nature of PFF-induced pathology.

Experimental flow design

Behavioral characterization

The PFF-induced mouse model showed impaired locomotor activity, muscle strength, and motor coordination, demonstrating robust late-onset motor deficits in this progressive synucleinopathy model.