July 29, 2014
The hallmark of an excellent researcher is an open mind.
That flexibility and openness is what led Nina Schor, M.D., Ph.D., the William H.
Eilinger Chair of Pediatrics at the University of
Rochester, to follow a hunch about a brain receptor – resulting in a
new mouse model that may give researchers a new avenue for testing drugs for autism.
Nature Publishing Groups’ Translational Psychiatry published the study
online today.
Schor had been studying p75 neurotrophin receptors in her
long-standing neuroblastoma research, but she also knew that
p75NTR is involved in the reaction to oxidative stress in the brain, which some
research posits plays a role in the development of autism. The receptor is also
prevalent in the developing brain and drops off as a child reaches 2 to 3 years
old, which is when autism symptoms often begin to appear. P75NTR stays present
in the typically developing cerebellum, hippocampus and basal forebrain, parts
of the brain that are anatomically abnormal in autism.
“Science doesn’t always travel in a straight line,” Schor
said. “Sometimes the importance of a scientific study in one field is what it
unexpectedly tells us about another field.”
While other researchers are focused on the proteins found
to be abnormal in patients with autism, Schor approached her investigation from
the opposite direction. She thought about what characteristics a protein would
have to have to be involved in processes thought to play a role in autism.
“That list of characteristics looked suspiciously like those we had found to be
associated with p75NTR.”
Then, Schor and her colleagues prevented mouse brains from
making p75NTR in one autism-associated type of cell in the cerebellum. What
they found was that not only does the mouse’s cerebellum resemble that of
children with autism, but the mouse also behaves much like children with
autism. They don’t engage in typical social behaviors of mice and instead,
ignore stranger mice and lack curiosity about their surroundings. They also
jump twice as much as typical mice, which is like a “stimming,” or
self-stimulatory, behavior typical in children with autism.
“Whether or not p75NTR turns out to be abnormal in
children with autism,” Schor explained, “these studies still hold the promise
of helping us explain the mechanisms behind the component behaviors of children
with autism.
Schor plans to continue the research, focusing on more
behavioral testing, finding evidence of whether children with autism have a
p75NTR deficit in their cerebellum and starting pharmaceutical testing to see
whether there is a drug that can replace the role p75NTR plays in that part of
the brain.
“It’s a long way from a mouse model to a successful
treatment in humans, but this is a good clue,” Schor said.
Schor’s co-authors on the paper describing the study are
Louis T. Lotta, Jr., Katherine Conrad, and Deborah Cory-Slechta, Ph.D., professor of Environmental Medicine. The study was funded
by the William H. Eilinger Endowment of Golisano Children’s Hospital at the
University of Rochester Medical Center and by a pilot grant from the Strong Children’s Research Center.
For Media Inquiries:
Heather Hare
(585) 273-2840
Email Heather Hare
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