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P Fernyhough

Publications and source records attributed to P Fernyhough.

At least 19 recordsLinked to original sources
PubMed2005

Neurotrophin-3 prevents mitochondrial dysfunction in sensory neurons of streptozotocin-diabetic rats.

Sensory neurons from streptozotocin (STZ)-diabetic rats exhibit depolarization of mitochondria and the related induction of reactive oxygen species has been proposed to contribute to the etiology of sensory polyneuropathy in diabetes. There is deficient neurotrophin-3 (NT-3)-dependent neurotrophic support of sensory neurons in diabetes and treatment of STZ-diabetic rats with NT-3 prevents neuropathological alterations in peripheral nerve. Therefore, we hypothesized that loss of NT-3 may contribute to mitochondrial dysfunction in sensory neurons in diabetic sensory neuropathy. The specific aim of this study was to determine whether treatment of STZ-diabetic rats with systemic NT-3 could prevent depolarization of the mitochondrial inner membrane potential (Deltapsi(m)). In vitro studies with cultured DRG neurons from control rats revealed that treatment with 50 ng/ml NT-3 for 6 h enhanced the Deltapsi(m), e.g., a higher polarized membrane potential, compared to untreated neurons (P < 0.05). Studies on DRG sensory neurons from control vs. STZ-diabetic rats demonstrated that NT-3 therapy prevented the diabetes-induced depolarization of Deltapsi(m) (P < 0.05) in parallel with normalization of diabetes-dependent deficits in sensory nerve conduction velocity. Furthermore, alterations in mitochondrial function in vitro and in vivo correlated with the level of activation/expression of Akt in DRG neurons.

Animals↗
PubMed2003

Enhanced activation of axonally transported stress-activated protein kinases in peripheral nerve in diabetic neuropathy is prevented by neurotrophin-3.

The objective was to determine whether stress-activated protein kinases (SAPKs) mediated the transfer of diabetes-induced stress signals from the periphery to somata of sensory neurons. Thus, we characterized axonal transport of SAPKs in peripheral nerve, studied any alteration in streptozotocin (STZ)-diabetic rats and examined effects of neurotrophin-3 (NT-3) on diabetes-induced events. We demonstrate that c-jun N-terminal kinase (JNK) and p38 are bidirectionally axonally transported at fast rates in sciatic nerve. In STZ-diabetic rats the relative levels of retrograde axonal transport of phosphorylated (activated) JNK and p38 were raised compared with age-matched controls (all data are in arbitrary units and expressed as fold increase over control: JNK 54-56 kDa isoforms, control 1.0 +/- 0.19, diabetic 2.5 +/- 0.26; p38, control 1.0 +/- 0.09, diabetic 2.9 +/- 0.52; both P < 0.05). Transport of total enzyme levels of JNK and p38 and phosphorylated extracellular signal-regulated kinase (ERK) was not significantly altered and anterograde axonal transport of phosphorylated JNK and p38 was unaffected by diabetes. The transcription factor ATF-2, which is phosphorylated and activated by JNK and p38, also exhibited elevated retrograde axonal transport in STZ-diabetic animals (control 1.0 +/- 0.07, diabetic 3.0 +/- 0.41; P < 0.05). Treatment of STZ-diabetic animals with 5 mg/kg human recombinant NT-3 prevented activation of JNK and p38 in sciatic nerve (phosphorylated JNK, control 1.0 +/- 0.09, diabetic 1.95 +/- 0.35, diabetic + NT-3 1.09 +/- 0.12; P < 0.05 diabetic versus others; phosphorylated p38, control 1.0 +/- 0.16, diabetic 4.7 +/- 0.9, diabetic + NT-3 1.19 +/- 0.18; P < 0.05 diabetic versus others). The results show that JNK and p38 are transported axonally and may mediate the transfer of diabetes-related stress signals, possibly triggered by loss of neurotrophic support, from the periphery to the neuronal soma.

Animals↗
PubMed2002

Diabetes-induced alterations in calcium homeostasis in sensory neurones of streptozotocin-diabetic rats are restricted to lumbar ganglia and are prevented by neurotrophin-3.

AIMS/HYPOTHESIS: In diabetic sensory polyneuropathy the earliest and most severe pathophysiology occurs in neurones with the longest axons. The aim of this study was to characterise a diabetes-induced neurodegenerative marker that was selective for sensory neurones with the longest axons. We studied alterations in calcium homeostasis since this occurs in other neurodegenerative diseases. METHODS: Sensory neurones were cultured from control and streptozotocin-diabetic rats, treated with or without human recombinant neurotrophin-3 (hrNT-3), and neurones from L4-L6 dorsal root ganglia (DRG) which exhibit the longest axons in vivo were compared with those from C5-L3 DRG. Fluorescent video-imaging was used to measure cytoplasmic calcium dynamics. RESULTS: Streptozotocin diabetes of 8 to 14 weeks, induced an increase in resting internal Ca(2+) concentration ([Ca(2+)](i)), from 67 +/- 7 nmol/l in small neurones and 79 +/- 9 nmol/l in big neurones obtained from control animals to 214 +/- 19 nmol/l in small neurones and 273 +/- 30 nmol/l in big neurones after 14 weeks of diabetes ( p < 0.05) in L4-L6 DRG cultures. Neurones from C5-L3 ganglia and non-neuronal cells were not affected. Treatment of 14-week streptozotocin-diabetic rats with subcutaneous injection of 5 mg/kg NT-3 normalised the increase in resting [Ca(2+)](i). The amplitudes induced by depolarisation, caffeine and ATP [Ca(2+)](i) responses were reduced in small ( < 30 microm diameter) but not big ( > 35 microm diameter) neurones of L4-L6 DRG from streptozotocin-diabetic animals; the C5-L3 DRG were not similarly affected and the changes in the L4-L6 DRG were corrected by NT-3 treatment. CONCLUSIONS/INTERPRETATION: Altered calcium homeostasis could be an early molecular marker linked to the onset of diabetic sensory neuropathy. This neurodegenerative index can be corrected by NT-3 therapy and should encourage further work aimed at understanding the mechanistic basis of these observations.

Adenosine Triphosphate↗
PubMed2002

Xestospongin C empties the ER calcium store but does not inhibit InsP3-induced Ca2+ release in cultured dorsal root ganglia neurones.

The action of Xestospongin C (XeC) on calcium concentration in the cytosol ([Ca2+]i) and within the lumen of endoplasmic reticulum (ER) ([Ca2+]L) was studied using cultured dorsal root ganglia (DRG) neurones. Application of 2.5 microM of XeC triggered a slow [Ca2+]i transient as measured by Fura-2 video-imaging. The kinetics and amplitude of XeC-induced [Ca2+]i response was similar to that triggered by 1 microM thapsigargin (TG). The [Ca2+]L was monitored in cells loaded with low-affinity Ca2+ indicator Mag-Fura-2. The cytosolic portion of Mag-Fura-2 was removed by permeabilisation of the plasmalemma with saponin. Application of XeC to these permeabilised neurones resulted in a slow depletion of the ER Ca2+ store. XeC, however, failed to inhibit inositol 1,4,5-trisphosphate (InsP3)-induced [Ca2+]L responses. We conclude that XeC is a potent inhibitor of sarco(endo)plasmic reticulum calcium ATPase, and it cannot be regarded as a specific inhibitor of InsP3 receptors in cultured DRG neurones.

Animals↗
PubMed2001

Nerve growth factor modulates the activation status and fast axonal transport of ERK 1/2 in adult nociceptive neurones.

Mature dorsal root ganglion cells respond to neurotrophins, and the intracellular signalling pathways activated by neurotrophins have been characterized in vitro. We have now used immunocytochemistry and Western blots to examine the expression and activation of extracellular signal-regulated protein kinase-1/2 (ERK) in rat dorsal root ganglion cells in vivo, using antisera to total (tERK) and phosphorylated (pERK) forms. This has revealed a number of novel findings. tERK immunoreactivity is present in most dorsal root ganglion cells but is expressed most strongly in small (nociceptive) cells and, surprisingly, is absent in a population of large cells that expressed trkB or trkC but mainly lack p75(NTR) immunoreactivity. In contrast pERK is prominent in a few trkA cells and in satellite glial cells, and is further increased by NGF treatment. tERK and pERK both undergo fast anterograde and retrograde axonal transport, indicated by accumulation at a sciatic nerve ligature, and NGF reduces the level of retrograde pERK transport.

Aging↗
PubMed2001

A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy.

The onset of diabetic neuropathy, a complication of diabetes mellitus, has been linked to poor glycemic control. We tested the hypothesis that the mitogen-activated protein kinases (MAPK) form transducers for the damaging effects of high glucose. In cultures of adult rat sensory neurons, high glucose activated JNK and p38 MAPK but did not result in cell damage. However, oxidative stress activated ERK and p38 MAPKs and resulted in cellular damage. In the dorsal root ganglia of streptozotocin-induced diabetic rats (a model of type I diabetes), ERK and p38 were activated at 8 wk duration, followed by activation of JNK at 12 wk duration. We report activation of JNK and increases in total levels of p38 and JNK in sural nerve of type I and II diabetic patients. These data implicate MAPKs in the etiology of diabetic neuropathy both via direct effects of glucose and via glucose-induced oxidative stress.

Animals↗
PubMed2000

Contraction-induced muscle fiber damage is increased in soleus muscle of streptozotocin-diabetic rats and is associated with elevated expression of brain-derived neurotrophic factor mRNA in muscle fibers and activated satellite cells.

The expression of brain-derived neurotrophic factor (BDNF) is elevated in the soleus muscle of streptozotocin-diabetic rats. To determine whether this diabetes-induced elevation was associated with or enhanced by muscle activity we have induced high-intensity muscle contraction by electrically stimulating the sciatic nerve. In 6-week diabetic rats, intense contraction of the soleus muscle resulted in a two- to four-fold elevation of BDNF mRNA and increased plasma levels of creatine kinase that were associated with severe focal muscle fiber damage and concomitant satellite cell activation. Focal muscle fiber damage and concomitant satellite cell activation were also observed in the soleus muscle of nonstimulated diabetic rats, but to a much lesser extent. No effects of muscle contraction, i.e., experimentally induced or during normal daily activity, on muscle fiber structure or BDNF mRNA expression were seen in diabetic extensor digitorum longus (EDL) muscle. Using a nonradioactive in situ hybridization technique for electron microscopy, the elevated expression of BDNF mRNA in the diabetic soleus muscle was localized within muscle fibers as well as activated satellite cells. This study shows that diabetic soleus muscle, in contrast to diabetic EDL and to soleus and EDL muscle of normal animals, is highly susceptible to contraction-induced damage. Intense contraction and the associated muscle fiber damage in the diabetic soleus muscle result in an upregulation of BDNF mRNA in muscle fibers and activated satellite cells, which may be involved in the restoration and/or maintenance of nerve/muscle integrity.

Animals↗
PubMed1999

Axonal transport of activating transcription factor-2 is modulated by nerve growth factor in nociceptive neurons.

The aim of this study was to determine whether axonal transport of activating transcription factor-2 (ATF2) occurs in adult sensory neurons, and whether this process is under neurotrophin control. Antisera to both total ATF2 and to the activated (i.e., phosphorylated) form were used for immunocytochemistry and Western blotting. ATF2 was localized to predominantly nociceptive dorsal root ganglion cells in adult rats and shown to accumulate proximal and distal to a sciatic nerve ligature as a result of axonal transport. Subcutaneous injection of nerve growth factor (NGF) decreased the levels of fast retrograde axonal transport of activated ATF2 by 97% (p < 0.05) and elevated levels of retrograde axonal transport of total ATF2 by twofold (p < 0.02). In contrast, blocking endogenous NGF using an anti-NGF antibody induced an elevation in retrograde axonal transport of activated ATF2 of 4. 5-fold (p < 0.05) and decreased retrograde axonal transport of total ATF2 by 72% (p < 0.05). NGF or anti-NGF treatment had no effect on the anterograde transport levels of total or activated ATF2. This study shows that signaling by target-derived NGF to the cell bodies of sensory neurons consists, in part, of the modulation of levels and activation status of a retrogradely transported transcription factor, ATF2.

Activating Transcription Factor 2↗
PubMed1999

Transforming growth factor-beta1 and glial growth factor 2 reduce neurotrophin-3 mRNA expression in cultured Schwann cells via a cAMP-dependent pathway.

The aim of the study was to determine which factors regulated the expression of neurotrophin-3 (NT-3) mRNA in cultured primary Schwann cells derived from sciatic nerve of neonatal rats. Treatment of primary Schwann cells with the adenylate cyclase activator, forskolin, or the cAMP agonist, 8-Br-cAMP, induced a significant reduction in NT-3 transcript levels. Transforming growth factor-beta1 (TGF-beta1) and glial growth factor 2 (GGF(2)) also reduced the levels of NT-3 mRNA in a dose and time-dependent manner. Treatment with nerve growth factor, brain-derived neurotrophic factor, NT-3, ciliary neurotrophic factor or interleukin-1beta was without effect. The TGF-beta1, GGF(2) and forskolin dependent reduction in NT-3 mRNA levels involved a destabilization of transcripts which was antagonised by co-treatment with cycloheximide. The cAMP-dependent protein kinase A (PKA) inhibitor, H-89, blocked the reduction in levels of NT-3 mRNA induced by TGF-beta1, GGF(2) and forskolin. The data show that the effects of TGF-beta1, GGF(2) and forskolin on the downregulation of NT-3 mRNA, at least in part, were due to a post-transcriptional event involving a labile protein intermediate under the control of PKA. The results suggest that the down-regulation of NT-3 mRNA in Schwann cells at a site of peripheral nerve damage may be mediated via a cAMP-dependent pathway and possibly involve neuroma-related elevations in TGF-beta1 and GGF(2).

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Elevated expression of neurotrophin-3 mRNA in sensory nerve of streptozotocin-diabetic rats.

Decreased expression of NT-3 mRNA in the sciatic nerve and leg muscles of streptozotocin (STZ)-diabetic rats has been associated with the pathogenesis of diabetic neuropathy. The aim of this study was to determine whether STZ-induced diabetes also affects the expression of NT-3 mRNA in the central and peripheral projections of sensory nerves. Competitive reverse transcription-polymerase chain reaction (cRT-PCR) was used to quantify the levels of NT-3 mRNA in the dorsal root, sural nerve, sciatic nerve and foot skin of age-matched and 12-week STZ-diabetic rats. Diabetes increased by 52% (P < 0.05) the expression of NT-3 mRNA in the dorsal root and sural nerve. It is proposed that diabetes-induced sensory nerve damage may elevate NT-3 mRNA production which may act as a source of neurotrophic support for sensory axons whose target-derived supply of NT-3 may be impaired.

Animals↗
PubMed1999

Focally administered nerve growth factor suppresses molecular regenerative responses of axotomized peripheral afferents in rats.

Effects of delivery of nerve growth factor, from a catheterized osmotic mini-pump to the proximal stump of a transected sciatic nerve, were compared with the effects of normal saline. A pilot measured retrograde axonal transport of nerve growth factor to determine a pump concentration which raised axonal transport ipsilaterally, but not contralaterally. The effects of this delivery over 12 days were then determined on expression of growth-associated protein-43, trkA, p75NTR and preprotachykinin A ipsilateral and contralateral to the pump in dorsal root ganglia at L4 and L5 (pooled). Ganglionic expression was measured both as messenger RNA and protein. Axotomy (saline pumps) increased growth-associated protein-43 messenger RNA (318 +/- 14%: all changes are percent of contralateral, non-axotomized ganglia with saline pumps) and immunoreactivity (431 +/- 43%). The increase was significantly less (P < 0.001) ipsilateral to nerve growth factor pumps (191 +/- 45%). Axotomy reduced expression of p75NTR (messenger RNA: 52 +/- 17%, P < 0.01; immunoreactivity: 74 +/- 3%, P < 0.05). These decreases were converted to increases by nerve growth factor delivery (respectively 143 +/- 40% and 281 +/- 67%; both P < 0.01). With trkA, axotomy decreased the expression of the messenger RNA (68 +/- 40%, P < 0.01) and of the primary translation product--110,000 mol. wt protein (55 +/- 12%, P < 0.01)--but not the fully glycosylated trkA protein (mol. wt 145,000). Nerve growth factor delivery did not affect trkA expression. Axotomy reduced messenger RNA for the substance P precursor, preprotachykinin A, to 42 +/- 17% (P < 0.01) and this reduction was prevented by nerve growth factor treatment. We suggest that the primary effect of nerve growth factor on axotomized C-fibres is not to promote regeneration, although that may be its secondary effect via an action on Schwann cells. It is possible that reduced neuronal sensitivity to nerve growth factor during regeneration is advantageous in suppressing nociception.

Animals↗
PubMed1999

Increased nerve growth factor mRNA in lateral calf skin biopsies from diabetic patients.

AIMS: This study set out to establish a novel procedure for the measurement of human nerve growth factor (NGF) messenger ribonucleic acid (mRNA) and to use this method to measure NGF expression in skin biopsies from control subjects and from patients with early neuropathies. NGF mRNA levels were related to functional measures of the competence of NGF-responsive nerves. METHODS: mRNA levels were measured by competitive reverse transcription with polymerase chain reaction amplification (cRT-PCR). Functional correlates of this observation were assessed by indices of thermal sensitivity--mediated by C-fibres, whose phenotype is regulated by NGF. RESULTS: NGF mRNA was increased in skin biopsies from 19 diabetic patients (5.12+/-3.88 (SD)) compared with samples from eight controls (1.57+/-0.95; P=0.001). Diabetic patients showed significantly (P < 0.001) diminished detection of cool and warm stimuli compared to age matched control group (n=24), but there were no differences in detection of heat as pain, or correlation with NGF mRNA levels. CONCLUSIONS: These findings suggest abnormally increased expression of NGF in diabetic neuropathy, which may represent a compensatory mechanism for impaired phenotype in NGF-responsive neurones.

Adult↗
PubMed1999

Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy.

Aberrant neurofilament phosphorylation occurs in many neurodegenerative diseases, and in this study, two animal models of type 1 diabetes--the spontaneously diabetic BB rat and the streptozocin-induced diabetic rat--have been used to determine whether such a phenomenon is involved in the etiology of the symmetrical sensory polyneuropathy commonly associated with diabetes. There was a two- to threefold (P < 0.05) elevation of neurofilament phosphorylation in lumbar dorsal root ganglia (DRG) of diabetic rats that was localized to perikarya of medium to large neurons using immunocytochemistry. Additionally, diabetes enhanced neurofilament M phosphorylation by 2.5-fold (P < 0.001) in sural nerve of BB rats. Neurofilaments are substrates of the mitogen-activated protein kinase (MAPK) family, which includes c-jun NH2-terminal kinase (JNK) or stress-activated protein kinase (SAPK1) and extracellular signal-regulated kinases (ERKs) 1 and 2. Diabetes induced a significant three- to fourfold (P < 0.05) increase in phosphorylation of a 54-kDa isoform of JNK in DRG and sural nerve, and this correlated with elevated c-Jun and neurofilament phosphorylation. In diabetes, ERK phosphorylation was also increased in the DRG, but not in sural nerve. Immunocytochemistry showed that JNK was present in sensory neuron perikarya and axons. Motoneuron perikarya and peroneal nerve of diabetic rats showed no evidence of increased neurofilament phosphorylation and failed to exhibit phosphorylation of JNK. It is hypothesized that in sensory neurons of diabetic rats, aberrant phosphorylation of neurofilament may contribute to the distal sensory axonopathy observed in diabetes.

Animals↗
PubMed1999

Neurotrophin-3 reverses nerve conduction velocity deficits in streptozotocin-diabetic rats.

The ability of neurotrophin-3 (NT-3) to reverse established nerve disorders was investigated in the peripheral neuraxis of streptozotocin-diabetic rats. Sciatic sensory and motor nerve conduction velocity deficits established after 2 months of diabetes were completely normalized by one further month of treatment with either NT-3 or insulin. None of these conduction velocity changes were associated with altered mean axonal caliber in the sciatic nerve. In the dorsal and ventral roots, mean axonal caliber was significantly decreased after 8 weeks of diabetes (both P < 0.05). Subsequently, one month of insulin, but not NT-3, treatment increased mean axonal caliber to age-matched control values. NT-3 treatment was also without effect on the significant (both P < 0.05) decrease in phosphorylated heavy neurofilament (NFH) subunits seen in dorsal and ventral roots of 12 week diabetic rats. In the sural nerve, diabetes attenuated a maturation-associated increase in mean axonal caliber over the first 8 weeks of diabetes, and induced atrophy between weeks 8 and 12 that was ameliorated by both NT-3 and insulin treatment. Reductions in sural nerve axonal caliber were associated with a tendency for elevation of both phosphorylated NFH levels in large fibers and the ratio of phosphorylated to nonphosphorylated NFH that was attenuated by NT-3. These data demonstrate that NT-3 corrects established sciatic nerve conduction deficits in diabetic rats in a manner independent of changes in axonal caliber in this nerve. Further, although NT-3 was without effect on decreases in axonal caliber and NFH subunit phosphorylation in the spinal roots, reversal of axonal caliber deficits in peripheral nerves of sensory fibers may involve NT-3-mediated normalization of aberrant neurofilament phosphorylation.

Animals↗
PubMed1998

Stimulation of nerve growth-factor and substance P expression in the iris-trigeminal axis of diabetic rats--involvement of oxidative stress and effects of aldose reductase inhibition.

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P < 0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P < 0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NFG, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes--a mechanism that might participate in iritis.

Aldehyde Reductase↗
PubMed1998

Effect of sciatic nerve crush on local and target tissue production of neurotrophin-3 transcripts in rats.

The effect of sciatic nerve crush in adult rats on neurotrophin-3 (NT-3) mRNA expression at the site of crush and in ipsilateral foot skin was studied using competitive reverse transcription-polymerase chain reaction (cRT-PCR). Mid-sciatic nerve crush resulted in a significant reduction in the expression of NT-3 mRNA in nerve segments distal to the injury site at 3 and 7 days (approximate 60% decrease; P < 0.01). The reduced NT-3 rnRNA expression started to increase at days 14 post-crush and returned towards control levels at 21 days following the crush. The nerve segment proximal to the crush site showed a similar changed pattern of NT-3 mRNA expression. The effects of denervation on NT-3 mRNA expression in foot skin were also studied. Reduced expression of NT-3 was observed by 7 days post-crush, with a 25% decrease observed by 14 days (P < 0.002). Levels of NT-3 mRNA had returned to normal by 21 days post-crush. The results show that changes in axon-Schwann cell contact do not account for the nerve crush induced loss, or subsequent recovery, of NT-3 mRNA expression in nerve.

Animals↗
PubMed1998

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

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.

Animals↗