Growth and survival in the nervous system
16, 1999, Gazette)
Dr. Karen Mearow
Karen Mearow, Medicine, is involved in basic research on the
developing and mature nervous system. In particular she is investigating
how the nervous system responds to injury why some cells
die and others survive and are able to regenerate damaged nerve
as the basic functional unit of the nervous system, are very
specialized cells that are responsible for all sensation and
direction of movement in the body. Each of these nerve cells
extends a projection (the axon) that connects it with either
muscle or other neurons; the axons are the route for information
sent both to and from the brain and spinal cord. It is these
connections among neurons and other tissues which provide the
necessary wiring for all functions of the nervous system. In
addition, in many cases these connections are also required for
the continued survival of the neurons.
injury to the nervous system, some nerve cells and their fibres
can be damaged to such an extent that they do not recover, while
others do recover and may be able to regenerate their fibres
under the right circumstances. However, since most neurons are
not able to divide to produce new neurons, neurons that are lost
following injury, disease or even normal aging are not replaced.
major focus of research in my field is understanding how to prevent
this loss and how to promote the regrowth of damaged nerve fibres
and the ultimate recovery of function, said Dr. Mearow.
One way of doing this is to understand the basic mechanisms
required for normal cell survival and fibre growth and how these
can be disrupted following stress or damage.
Mearows work centres on a group of compounds known as the
neurotrophins, in particular nerve growth factor (NGF). The developing
nervous system requires these factors for their early differentiation
and survival as well as the formation of appropriate connections
with their target tissues (e.g. other neurons, muscle, skin).
For many types of neurons this dependence on the neurotrophins
for both survival and formation and maintenance of connections
extends through adulthood. However, for one group of neurons,
the sensory neurons in the peripheral nervous system, while the
very young neurons require the factors for survival, the older
neurons do not.
area of Dr. Mearows research is to investigate how NGF
regulates this survival response as well as being involved in
promoting nerve fibre regeneration. She is concerned with whether
the young neurons use the same signaling pathways as the adult
neurons. A signaling pathway defines how the neuron will respond
to the growth factor. The NGF binds to specific receptors on
the nerve cell surface and this sets off a series of biochemical
steps that result in a particular cellular response whether
it be survival or neurite initiation.
like turning on a radio and getting a sound at the end,
she explained. You can turn the radio on with the power
switch, but you also have the choice of a number of different
stations depending upon where you live and you can also turn
the volume up or down.
our system, the receptors are defined and many of the individual
components of the signaling pathways are also known. But even
though the young and adult neurons have the same receptors and
many of the same signaling components, they dont require
the same pathways for survival. We want to know why this is
we want to find the key point where if you block one component,
you lose the survival or growth response
Mearow describes her work as similar to putting together a puzzle,
except that sometimes you dont know what the pieces are
or how they fit together. Working primarily with neurons in tissue
cultures, she and her research group have found that neonatal
sensory neurons require NGF for survival and that a particular
signaling pathway is activated and required for this response.
In contrast, within one to two weeks after birth of the animal,
these same neurons no longer need NGF to keep them alive
they do need it for putting out their axons, however. Although
the same signaling pathways are active in the mature neurons,
they appear to be activated differently and it may be that other
pathways interact with the NGF-activated signals to keep these
adult neurons alive.
other interpretation is that there are both life
and death pathways, said Dr. Mearow. In
the young neurons the death pathway may be the default
and these cells require activation of the life pathway
by NGF to suppress the death pathway. In the adult
neurons, it is possible that the death pathway is
no longer as active, and therefore signaling along the NGF life
pathway is no longer critical for survival.
NGF and other trophic (nutritional) factors are important in
the normal development and function of the nervous system as
well as during aging or after injury, Dr. Mearow hopes that her
research will contribute to understanding how neurons respond
to damage and how trophic factors can be used to keep cells alive
longer or enhance nerve regeneration.
Mearows research recently received a three-year Medical
Research Council of Canada grant, and her funding from the Natural
Sciences and Engineering Research Council of Canada has been
renewed for a further four years.