Gary R. Coulton

Effect of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres.

We investigated whether neurotrophin‐4 (NT‐4) and brain‐derived neurotrophic factor (BDNF) affected the reinnervation of slow and fast motor units. Neurotrophin‐impregnated or plain fibronectin (FN) conduits were inserted into a sciatic nerve gap. Fast extensor digitorum longus (EDL) and slow soleus muscles were collected 4 months postsurgery. Muscles were weighed and fibre type proportion and mean fibre diameters were derived from muscle cross‐sections. All fibre types in muscles from FN animals were severely atrophied and this correlated well with type 1 fibre loss and atrophy in soleus and type 2b loss and atrophy in EDL. Treatment with NT‐4 reversed soleus but not EDL mass loss above the FN group by significantly restoring type 1 muscle fibre proportion and diameters towards those of normal unoperated animals. BDNF did not increase muscle mass but did have minor effects on fibre type and diameter. Thus, NT‐4 significantly improved slow motor unit recovery, and provides a basis for therapies intended to aid the functional recovery of muscles after denervating injury.

Cytochemical evidence for functional zonation of parietal cells within the gastric glands of the mouse

SummaryParietal cells in the luminal segments of mouse gastric glands show high activity of acid-secreting potassium-dependent adenosine triphosphatase (H+, K+-ATPase) and of nicotinamide adenine dinucleotide-linked isocitrate dehydrogenase (NAD-ICDHase) and malate dehydrogenase (MDHase) but low activity of succinate dehydrogenase (SDHase). This pattern of activity is reversed in the basal segments of the same glands. These results and previous morphological findings support the conclusion that luminal segment parietal cells are much more active in hydrochloric acid secretion than those of the basal segment. The origin of this zonation may be either cellular deterioration with age or some more specific form of regulation of parietal cell metabolism.

Regulation of major histocompatibility complex class II synthesis by interleukin-10.

We have shown previously that interleukin‐10 (IL‐10) blocks the development and T‐cell stimulatory capacity of human monocyte‐derived dendritic cells, without apparently down‐regulating the surface expression of co‐stimulatory molecules or human leucocyte antigen (HLA) molecules. In the majority of donors (60%), the cell surface levels of HLA‐DR actually increased upon IL‐10 treatment. Here we have shown that IL‐10 does not regulate HLA‐DR transcription as assessed by polymerase chain reation. Epifluorescence microscopy analysis showed that IL‐10 primarily increased the intracellular pool of HLA‐DR. In fact, IL‐10 directly increased HLA‐DR protein synthesis. However, IL‐10 did not significantly alter the synthesis of invariant chain (Ii), which plays a crucial role in the assembly, transport and loading of newly formed HLA class II molecules, nor the amount of Ii reaching the cell‐surface. In contrast, IL‐10 increased the amount of HLA‐DR‐bound Iip33 shortly after the HLA‐DR complex assembly. We postulate that, upon IL‐10 treatment, immature Ii‐associated HLA II molecules can still transit to the cell surface as they do in immature dendritic cells and recycle to the intracellular space, where they accumulate. A higher proportion of Ii‐associated HLA‐DR, coupled to increased membrane recycling, may contribute to the lower T‐cell stimulatory capacity of IL‐10‐treated dendritic cells.

Differential tyrosine kinase C mRNA distribution in extensor digitorum longus and soleus motoneurons in adult rats: effect of axotomy and neurotrophin-3 treatment.

Delivery of neurotrophin-3 (NT-3) to severed sciatic nerves results in specific normalization of atrophied fast 2b gastrocnemius muscle fibres, and promotes preferential neuromuscular junction maturation of fast extensor digitorum longus (EDL). To investigate the selective influence on fast muscle reinnervation due to NT-3 delivery, we analyzed tyrosine kinase C (trkC) mRNA differential expression in EDL and slow soleus motor pools of unoperated rats and at 1-week post-axotomy. Motoneurons (Mns) were identified using retrograde tracers. TrkC mRNA quantification was estimated by silver grain counting. TrkC mRNA expression was higher in EDL than in soleus Mns in unoperated rats. Axotomy decreased trkC mRNA expression only in EDL Mns, this downregulation being prevented by NT-3. These results suggest that differential expression of trkC receptor is the morphological correlate of the preferential effect of NT-3 upon EDL Mns.