Decreased neurotrophin-3 expression in skeletal muscles of streptozotocin-induced diabetic rats

Ihara, Chihiro; Shimatsu, Akira; Mizuta, Haruo; Murabe, Hiroyuki; Nakamura, Yoshio; Nakao, Kazuwa

doi:10.1016/s0143-4179(96)90018-9

Cited by 26 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown reduced mRNA expression in soleus muscle and gastrocnemius muscle [26,27], but the inclusion of NT-3 protein measurements considerably strengthens the case for reduced NT-3-dependent neurotrophic support in diabetes.…”

Section: Discussionmentioning

confidence: 79%

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

1998

View full text Add to dashboard Cite

Neurotrophin-3 (NT-3) is a member of a structurally related group of neurotrophic peptides that include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4) and that combine to regulate the development and maintenance of the vertebrate peripheral nervous system [1,2]. A role for NGF in the aetiology of diabetic neuropathy was suggested following demonstration of deficient retrograde axonal transport of 125 I-labelled NGF in sciatic [3] and ileal mesenteric[4] nerves of diabetic rats. Recent studies have established a clear relationship between deficient NGF expression in target tissues of the lower limb [5], reduced retrograde transport of endogenous NGF to the lumbar dorsal root ganglia (DRG) [6,7] and reduced expression of the neuropeptides, substance P and calcitonin gene-related peptide (CGRP), which are neuronal targets for NGF in C-fibers [8,9]. These experimental observations indicate a mechanism for suppression of small calibre C-fibre activity in diabetic sensory neuropathy and clinical evidence supports such an involvement in general cases [10].Large calibre myelinated sensory fibres undergo degeneration in human diabetic neuropathy [11]. In experimental models of diabetes fibre degeneration is not well characterised; however, large myelinated sensory fibres do undergo loss of calibre [12] and are implicated in the occurrence of tactile allodynia, a feature of abnormal b-mechanoreceptor function [13]. In the clinical situation these abnormal proper- Diabetologia (1998) Summary 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. [Diabetologia (1998) 41: 300±306]

show abstract

Section: Discussionmentioning

confidence: 79%

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

1998

View full text Add to dashboard Cite

show abstract

“…Previous studies have reported that the level of NT-3 mRNA increases in the sensory nerves of diabetic rats (Cai et al, 1999), and the concentrations of NT-3 in the suprabasal epidermis, where many unmyelinated small sensory nerves terminate, is significantly increased in diabetic patients (Kennedy et al, 1998). Other studies have also demonstrated that the target-derived NT-3, which is retrogradely transported to support myelinated large nerve fibers, decreases in diabetic animals (Ihara et al, 1996;Fernyhough et al, 1998). Taken together, these findings suggest that in diabetic rats the NT-3 increase in the small-size neurons may be compensated to maintain the level of NT-3 responsive neurons due to the loss of NT-3 supply from skeletal muscles.…”

Section: Discussionmentioning

confidence: 96%

Early expression of injury-induced neuropeptide Y in primary sensory neurons and the cuneate nucleus in diabetic rats with median nerve transection

Lin

Tsai

Chen

et al. 2010

Journal of Chemical Neuroanatomy

View full text Add to dashboard Cite

“…Systemic NT-3 treatment has also been shown to prevent toxin-induced peripheral neuropathies (20,21). Demonstration of altered expression of NT-3 and its receptors in DRG, nerve, and muscle in STZ-induced diabetic animals suggests that loss of NT-3-dependent neurotrophic support may contribute to the pathogenesis of diabetic neuropathy (22)(23)(24). In the galactose-fed rat model of diabetes and in the STZ-induced diabetic rat, NT-3 treatment prevents axonal atrophy of sensory nerves and slowing of sensory nerve conduction velocity (SNCV) in the sciatic nerve (3,25).…”

mentioning

confidence: 99%

Neurotrophin-3 Prevents the Proximal Accumulation of Neurofilament Proteins in Sensory Neurons of Streptozocin-Induced Diabetic Rats

et al. 2003

View full text Add to dashboard Cite

The relation between neurofilament expression and/or phosphorylation in the proximal versus distal components of the sensory peripheral neuraxis was studied and related to disorders in structure and function of the distal axon of streptozocin (STZ)-induced diabetic rats studied for 14 weeks. The ability of neurotrophin-3 (NT-3) to prevent abnormalities in neurofilament biology was also investigated. Compared with age-matched controls, neurofilament heavy (NF-H) (3.3-fold) and neurofilament medium (NF-M) (2.5-fold), but not neurofilament light (NF-L), subunits accumulated in the proximal axon of sensory neurons of the lumbar dorsal root ganglia (DRG) in untreated diabetic rats. Neurofilament accumulation was prevented by NT-3. Smalland large-diameter sensory neurons exhibited elevated levels of NF-H protein accumulation and phosphorylation in the DRG of untreated diabetic rats, levels that were ameliorated by NT-3. The sural nerve of untreated diabetic rats showed a 50% decrease in the levels of NF-H and NF-M, but not NF-L, subunits; NT-3 only partially normalized the defect in NF-M expression. These observations were associated with significant lowering of motor and sensory nerve conduction velocity but no alteration in the mean axonal diameter of myelinated axons in the sural nerve in untreated diabetic rats. It is proposed that the accumulation of NF-H and NF-M subunits in the proximal axon is an etiologic factor in the distal axon degeneration observed in diabetes. [NF-L]). In the streptozocin (STZ) and BB rodent models of type 1 diabetes, structural abnormalities in peripheral nerve include decreased axonal caliber or axonal dwindling (1-3). Studies in type 1 diabetic rats show reduced expression of neurofilaments in sensory neurons (1,4,5), reduced axonal transport of neurofilament in sensory axons (6), loss of neurofilament in distal nerve (1-3,7), and abnormal neurofilament phosphorylation in the dorsal root ganglia (DRG), spinal cord, and sciatic nerve (8 -11). Aberrant phosphorylation of NF-H and NF-M subunits in DRG of STZ-and BB-diabetic rats is associated with activation of c-jun NH 2 -terminal kinase (JNK) (10). The stress-activated protein kinases (SAPKs: extracellular signal-regulated kinase [ERK], JNK, and p38) are well-characterized proteins that phosphorylate neurofilaments and are activated by hyperglycemia and oxidative stress in cultured sensory neurons (11-13).Nerve crushϪinduced loss of neurofilament expression in the small-to-medium subpopulation of neurons in the DRG is ameliorated by nerve growth factor treatment (14,15). Sequestration of the high-affinity receptor for neurotrophin-3 (NT-3) results in motor and sensory nerve conduction velocity (NCV) deficits similar to those that develop after nerve transection (16). Exogenous NT-3 provided after physical nerve injury can prevent and reverse a range of injury-evoked responses (16 -18) and also enhance subsequent regeneration (19). Systemic NT-3 treatment has also been shown to prevent toxin-induced peripheral neuropathies (20,21). Dem...

show abstract

Decreased neurotrophin-3 expression in skeletal muscles of streptozotocin-induced diabetic rats

Cited by 26 publications

References 18 publications

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

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

Early expression of injury-induced neuropeptide Y in primary sensory neurons and the cuneate nucleus in diabetic rats with median nerve transection

Neurotrophin-3 Prevents the Proximal Accumulation of Neurofilament Proteins in Sensory Neurons of Streptozocin-Induced Diabetic Rats

Contact Info

Product

Resources

About