Target tissue production and axonal transport of neurotrophin-3 are reduced in streptozotocin-diabetic rats.

Abstract:

:Neurotrophin-3 (NT-3) acts as a target-derived neurotrophic factor for large calibre sensory neurones and plays a role in the maintenance of the adult phenotype of proprioceptive and mechanoreceptive fibres. Large fibre sensory neuropathy is common in diabetes mellitus and the aim of this study was to determine whether endogenous NT-3-dependent neurotrophic support was sub-optimal in the streptozotocin-diabetic rat. NT-3 gene expression was analysed by Northern blotting and ELISA in hindlimb skeletal muscle and found to be decreased by up to 70% (p < 0.05) in rats with 4-6 weeks of diabetes compared to aged-matched controls. Treatment of other diabetic rats with insulin prevented development of deficits of both NT-3 protein and of its mRNA. The deficits in target tissue production of NT-3 were coincident with significant decreases in its anterograde and retrograde axonal transport in sciatic nerve at 6 weeks of diabetes. The mRNA expression in lumbar dorsal root ganglia of the specific receptor for NT-3, trkC, was also down-regulated at 12 weeks of diabetes by 50% (p < 0.05). The observed decreases in NT-3 target tissue production and related axonal transport suggest that large calibre sensory neurones expressing trkC may be receiving sub-optimal neurotrophic support in experimental diabetes.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Fernyhough P,Diemel LT,Tomlinson DR

doi

10.1007/s001250050907

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

300-6

issue

3

eissn

0012-186X

issn

1432-0428

journal_volume

41

pub_type

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