Progress Toward an Animal Model of PSP
Stewart Clark, PhD, University of Buffalo
Having animal models in the lab – new model of PSP
- Trying to find out where Tau’s hideout is—Why do we need an Animal Model?
- To help reverse or stop the protein aggregation
- To improve longevity, and QOL
- Without a model specific to PSP, we cant look for drugs to help with these symptoms
Progressive model – take a healthy animal and “give them PSP”
- What should this model look like?
- Postmortem brain characteristics
- Peduncuulopontine Tegmentum loss (pptg)
- Ventricular enlargement
- Substantia nigra loss
- Abnormal protein aggregates
- Behavioral
- Startle deficits
- Motor deficits
- Cognitive deficits
- Postmortem brain characteristics
- Hypothesized spread of tau in PSP
- As the disease progresses, we get higher concentrations in more areas
- We want to control the amount of areas it spreads to
- Blunts Acoustic Startle Response (Multiple tests performed on the rats)
- When they are exposed to repeated loud stimulation, PSP patients seemed not to jump
- Rats with this lesion (neurons remove) have different behaviors that are abnormal
- Substantia Nigra Loss
- Overlap with Parkinson’s
- Overtime, pptg lesions produce a significant loss of SN neurons. Although at 14 months post lesion, the loss is not to the degree seen in PSP.
- When they are exposed to repeated loud stimulation, PSP patients seemed not to jump
- Still in the process of looking for cognitive deficits in animal models
- Produce abnormal tau and its spread
- Accelerate the progression of deficits