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Ciliary neurotrophic factor is upregulated during axonal sprouting in the rat magnocellular neurosecretory system.

The response of the magnocellular neurosecretory system (MNS) to partial denervation is characterized by an initial period of axonal degeneration followed by the near complete restoration of axon density within the neural lobe (NL) by 30 days post-denervation (PD). We have utilized this preparation to investigate the expression of neurotrophins during the well defined periods of cellular and axonal degeneration and axonal sprouting. In this regard, ciliary neurotrophic factor (CNTF) has been reported to act as a survival and sprouting factor for axotomized magnocellular neurons in vitro. These observations have led us to investigate the potential role for CNTF, and its cellular sources, during collateral axonal sprouting in the MNS of the rat in vivo. Within the axotomized hypothalamic supraoptic nucleus (SON), a significant increase in the intensity and extent of CNTF immunoreactivity (CNTF-ir) was observed between 1 and 10 days PD. In the contralateral non-axotomized SON a significant but less pronounced increase was also observed over the same period. Subsequent dual-label fluorescence confocal microscopy demonstrated that the CNTF-ir within the SON is localized exclusively to astrocytes. In situ hybridization histochemical analysis (ishh) confirmed an upregulation of CNTF message had occurred concomitantly with the increased CNTF-ir. additionally, ishh studies show a distinct upregulation of the CNTF receptor alpha in the non-axotomized, sprouting SON. Within the denervated NL where axonal sprouting occurs a similar increase in CNTF-ir was observed. Subsequent stereometric assessment of the numbers of CNTF-ir cells demonstrated a highly significant increase by 3 days PD reaching 130% of control values by 10 days post-denervation. The cell numbers remained elevated at 30 days PD suggesting that CNTF may play a role in the sprouting process within the axon terminal field. However, in the NL the CNTF-ir cells did not co-localize with GFAP indicating CNTF is not expressed by resident pituicytes. The morphological characteristics of the CNTF-ir cells in the NL suggests a perivascular phenotype. Studies are currently underway to un-equivocally establish the phenotype of these cells. These studies were supported by BRIN-NCRR-P20-RR16471 and NIH RO3-MH64171-01 to JAW.

John Watt *

Department of Anatomy & Cell Biology, University of North Dakota, School of Medicine and Health Sciences, Grand

Forks, ND 58202
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Title Annotation:ND BRIN Professional Session: Crystal Ballroom
Author:Watt, John
Publication:Proceedings of the North Dakota Academy of Science
Geographic Code:1USA
Date:Apr 1, 2004
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