Source: Yale University (http://www.yale.edu)
Date: Posted 10/22/99
Yale Study Shows Way To Re-Stimulate Brain Cell Growth
Results Could Boost Understanding Of Alzheimer's, Other Brain Disorders
New Haven, Conn. -- Yale scientists have discovered that the growth of brain
cells, which normally ends in adolescence, can be re-stimulated in mature
neurons with a molecular mechanism known as Notch signaling.
Because Notch signaling also may be involved in the progression of
degenerative diseases like Alzheimer's, the results published in the October
22 issue of Science could help scientists find ways to treat, or even
prevent, this and other brain disorders.
"Our results not only help in our understanding of brain development, but
they also have considerable implications for designing new treatments for
many neurological disorders," said Pasko Rakic, M.D., the study's principal
investigator.
"One of the hallmarks of Alzheimer's disease is the alteration of brain cell
processes that can lead to irreversible memory loss and cognitive abilities
characteristic of the disorder," Rakic said. "While we are still trying to
determine what role Notch signaling plays in Alzheimer's, the results of
this study could open possibilities for treating and preventing these kinds
of brain disorders."
As the brain develops, neurons grow rapidly by extending
neurites --dendrites and axons -- which make millions of connections from
birth up until adolescence, when the connections in the cerebral cortex
begin to stabilize. As stabilization occurs, long term memory is acquired,
allowing people to remember things throughout their lives. This new study
provides a clue to how the transition from growth to stability might occur.
"We have identified the signaling pathway involved in the switch from growth
to stability, as well as the associated molecules that can turn the switch
on and off," said Rakic, professor and chair of neurobiology at Yale Medical
School.
The main element of the signaling pathway is the Notch receptor, which was
first described in studies at Yale in the 1940s and was then cloned at Yale
in the 1980s, but its role in adult brain cells has not been identified
until now.
In their study, Rakic and his colleagues found a new and unexpected role for
the Notch gene and related molecules. The Notch receptors are present in
neurons and their specialized processes called neurites. Neurons of the
cerebral cortex -- a thin sheet of gray matter on the surface of the
brain --grow by extending their neurites and forming connections, both of
which are accompanied by an increase in activity of the Notch signaling
pathway. The Notch signaling pathway gradually inhibits the extension of
neurites and keeps them stable in maturity.
By inhibiting Notch activity in mature neurons, the team was able to reverse
this state of stability and re-initiate neuron growth. These findings
suggest that the Notch signaling pathway prevents neurites from forming new
connections in the adult cerebral cortex, and therefore plays a role in
regulation of growth and stability of neural connections.
In Alzheimer's disease, a mutation of the gene presenilin is responsible for
the early-onset of the disease. These new results provide a clue to how
mutations in presenilin, which is known to affect Notch signaling, may
contribute to alteration of neurites found in the disease.
Rakic's research team included Yale graduate student Nenad Sestan and Spyros
Artavanis-Tsakonas, professor of cell biology at Harvard.
Editor's Note: The original news release can be found at
http://www.yale.edu/opa/newsr/99-10-20-01.all.html
