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Volume 16, Number 23,
Issue of December 1, 1996
pp. 7469-7477
Copyright ©1996 Society for Neuroscience
Intrinsic Injury Signals Enhance Growth, Survival, and
Excitability of Aplysia Neurons
Received July 17, 1996; revised Sept. 10, 1996; accepted Sept. 12, 1996.
Richard T. Ambron1,
Xiao-Ping Zhang1,
John D. Gunstream2,
Michael Povelones1, and
Edgar T. Walters2
1 Department of Anatomy and Cell Biology,
Columbia University, New York, New York 10032, and
2 Department of Integrative Biology, University of Texas at
Houston, Medical School, Houston, Texas 77030
Neurons undergo extensive changes in growth and
electrophysiological properties in response to axon injury. Efforts to
understand the molecular mechanisms that initiate these changes have
focused almost exclusively on the role of extrinsic signals, primarily neurotrophic factors released from target and glial cells. The objective of the present investigation was to determine whether the
response to axonal injury also involves intrinsic axoplasmic signals.
Aplysia neurons were removed from their ganglia and
placed in vitro on a substratum permissive for growth,
but in the absence of glia and soluble growth factors. Under these
conditions, neurites emerged and grew for ~4 d. Once growth had
ceased, the neurites were transected. In all, 46 of 50 cells
regenerated, either by resorbing the remaining neurites and elaborating
a new neuritic arbor or by merely replacing the neurites that had been
severed. Cut cells also exhibited enhanced excitability and,
paradoxically, prolonged survival, when compared with uninjured
neurons. These findings indicate that axons contain intrinsic molecular
signals that are directly activated by injury to trigger changes
underlying regeneration and compensatory plasticity.
Key words:
axotomy;
cellular stress;
regeneration;
sensitization;
axoplasm;
retrograde transport;
intracellular recording
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