Parkinson's Disease
To induce Parkinsonism in rodents for the identification and development of new therapies, we utilize the rotenone rat model. Our experience with protocols that offer dose-related, graded dopaminergic depletions and the ability to assess endpoints at the behavioral, biochemical and anatomical level, provides opportunities to study the effects of an NCE against these endpoints.
Models
Rotenone model,
In the rat, the systemic injection of rotenone results in a variety of behavioral, biochemical and histopathological changes which bear parallels with changes in Parkinson’s Disease. Together these measures provide multiple endpoints to assess the effect of an NCE in this model.
A 10-12 daily regimen of rotenone (2.75 – 3 mg/kg IP) produces significant effects on tasks of neurological function. The most robust changes are measured using rearing in open field, postural instability and beam walking. Tremor, hypolocomotion, catalepsy are inconsistently affected by rotenone treatment.
Read the full description: Rotenone model
MPTP model,
In the MPTP model, MPTP is converted to MPP+ and selectively taken up into dopaminergic neurons, where it inhibits mitochondrial complex I, depleting striatal dopamine. Acute and sub-chronic dosing regimens support screening, efficacy and neuroprotection studies.
Platforms used
Molecular Biomarkers & Histology Molecular biomarkers and tissue biomarker expression
Electroencephalography (EEG) In-vivo rodent telemetry
MoSeq AI-powered motion sequencing
Operant Platform Motivation, impulsivity, attention, cognition, memory
PK/PD Studies Endpoints for lead optimization
PK-Bridge PK studies for discovery budgets
Cognitive Assessment Aged-dog memory and cognitive decline
Transgenics Genetically modified mice
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