SCoBIRC FACULTY

Malathi Srivatsan, Ph.D.

Research Assistant Professor,
Department of Physiology

Ph.D., All India Institute of Medical Sciences, 1977.

Research Interests

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.

Representative Publications

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.