BSN PSP/CBD Conference – Stewart Clark

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
  • 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.
  • Still in the process of looking for cognitive deficits in animal models
    • Produce abnormal tau and its spread
    • Accelerate the progression of deficits