Malathi Srivatsan, Ph.D.
Research Assistant Professor,
Department of Physiology
Ph.D., All India Institute of Medical Sciences, 1977.
Role of Cholinergic Components in Neuroregeneration
Differentiated neurons are mostly post-mitotic and hence have to be
functionally viable throughout the life of the organism. Neurons strive
to maintain their functional competence by continually adapting and
responding to the ever changing demands imposed on them. One critical
expression of such neuronal plasticity is the ability of the neurons
to grow processes and make synaptic contacts during development as well
as after injury to attain functional recovery during regeneration. I
am interested in studying neuronal responses and the influence of the
immediate environment of the neuron on such responses after injury and
during regeneration to find means of promoting axonal growth and restoration
of functional synaptic contacts. Currently I am studying the role of
acetylcholinesterase (AChE) in neuro-regeneration AChE is well known
as an enzyme that hydrolyzes the neurotransmitter acetylcholine at the
cholinergic synapse. Yet its presence in undifferentiated and non-cholinergic
neurons as well as its increased expression in many parts of the developing
nervous system during neurite growth suggest that it has an additional
function as a growth factor. My experiments using primary cultures of
dissociated neurons have provided direct evidence for a non-classical
role of AChE in promoting neurite growth. At present I am investigating
the mechanism of action of the specific sites of the AChE molecule in
promoting neurite growth using site-specific inhibitors and antibodies
of AChE. I am using in vivo and in vitro models of neuroregeneration,
employing techniques of dissociated cell culture, nerve crush, imaging
and morphometry to measure neurite growth during regeneration; Western
blot analysis and immunocytochemistry to monitor protein expression;
Receptor binding analysis using radiolabelled AChE and AChE-coated fluorescent
beads to examine AChE-neuronal interaction. Results of our studies will
help understand how AChE stimulates regeneration in DRG neurons and
will help me extend these studies to investigate whether AChE can enhance
functional recovery in SCI. Knowledge of the mechanism of action of
a ubiquitous neurotrophic factor which is readily available in adult
CNS neurons, cerebrospinal fluid, macrophages and erythrocytes will
help significantly in developing strategies to promote growth and thus
accelerate functional recovery following SCI.
Srivatsan, M. (1999) Organophosphates inhibit acetylcholinesterase and
impair neurite growth of cholinergic neurons in Aplysia. Chemico-Biological
Interactions, 120: 371-378,1999.
Srivatsan, M. and Peretz, B. (1997) Acetylcholinesterase promotes regeneration
of neurites in cultured adult neurons. Neuroscience, 77:921-931.
Srivatsan, M. and Peretz, B. (1996) Effects of acetylcholinesterase
inhibition on behavior is age-dependent in freely moving Aplysia. Behav.
Brain Res. 77: 115-124.
Srivatsan, M. and Peretz, B. (1995) Neurotrophic function of circulating
acetylcholinesterase in Aplysia. pp 449-450, In "Enzymes of the
Cholinesterase family" Eds. A.S. Balasubramanyan, B.P. Doctor,
P. Taylor and D.M. Quinn,Plenum Publishing CO., New York.
Srivatsan, M., Peretz, B., Hallahan, B. and Talwalker, R. (1992) Acetylcholinesterase
and other hemolymph proteins change with age in Aplysia. J. Comp. Physiol.
B. 162: 29-37.
Kindy, M.S., Srivatsan, M. and Peretz, B. (1991) Age-related differential
expression of Neuropeptide mRNAS in Aplysia. Neuroreport 2:465-468.
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