JN  AJP: Regulatory, Integrative and Comparative Physiology
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J Neurophysiol 90: 2232-2239, 2003. First published June 18, 2003; doi:10.1152/jn.00347.2003
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Anesthetic Treatment Blocks Synaptogenesis But Not Neuronal Regeneration of Cultured Lymnaea Neurons

Alyson J. Woodall1,*, Hiroaki Naruo2,3,*, David J. Prince3, Zhong Ping Feng3, William Winlow1, Mayumi Takasaki2 and Naweed I. Syed3

1 Biological Sciences, University of Central Lancashire, Preston, Lancashire PR1 2HE, United Kingdom; 2 Department of Anesthesiology, Miyazaki Medical College, Miyazaki 889-1692, Japan; 3 Respiratory and Neuroscience Research Groups, Department of Cell Biology and Anatomy/Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada

Submitted 9 April 2003; accepted in final form 12 June 2003

Trauma and injury necessitate the use of various surgical interventions, yet such procedures themselves are invasive and often interrupt synaptic communications in the nervous system. Because anesthesia is required during surgery, it is important to determine whether long-term exposure of injured nervous tissue to anesthetics is detrimental to regeneration of neuronal processes and synaptic connections. In this study, using identified molluscan neurons, we provide direct evidence that the anesthetic propofol blocks cholinergic synaptic transmission between soma-soma paired Lymnaea neurons in a dose-dependent and reversible manner. These effects do not involve presynaptic secretory machinery, but rather postsynaptic acetylcholine receptors were affected by the anesthetic. Moreover, we discovered that long-term (18–24 h) anesthetic treatment of soma-soma paired neurons blocked synaptogenesis between these cells. However, after several hours of anesthetic washout, synapses developed between the neurons in a manner similar to that seen in vivo. Long-term anesthetic treatment of the identified neurons visceral dorsal 4 (VD4) and left pedal dorsal 1 (LPeD1) and the electrically coupled Pedal A cluster neurons (PeA) did not affect nerve regeneration in cell culture as the neurons continued to exhibit extensive neurite outgrowth. However, these sprouted neurons failed to develop chemical (VD4 and LPeD1) and electrical (PeA) synapses as observed in their control counterparts. After drug washout, appropriate synapses did reform between the cells, although this synaptogenesis required several days. Taken together, this study provides the first direct evidence that the clinically used anesthetic propofol does not affect nerve regeneration. However, the formation of both chemical and electrical synapses is severely compromised in the presence of this drug. This study emphasizes the importance of short-term anesthetic treatment, which may be critical for the restoration of synaptic connections between injured neurons.


Address for reprint requests and other correspondence: N. I. Syed, Respiratory and Neuroscience Research Groups, Dept. of Cell Biology and Anatomy/Physiology and Biophysics, Faculty of Medicine, University of Calgary (E-mail: nisyed{at}ucalgary.ca).







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