Terje lomo biography template

Intramuscular injection of ADV vectors also caused transduction of spinal motoneurons and dorsal root ganglion cells. However, only neurons innervating the injected muscle were transduced, as shown by co-injection of a retrograde axonal tracer. In adult male rats it is therefore possible to transduce fast or slow spinal motoneurons and muscle fibers selectively since in these animals, the extensor digitorum longus and soleus muscles contain almost exclusively fast or slow motor units, respectively.

In rats, AAV vectors transduced muscle fibers in the predominantly fast extensor digitorum longus but not in the predominantly slow soleus muscle. We did not observe any transduction of spinal motoneurons following intramuscular injection of AAV vectors. These results show that physiologically and clinically important subpopulations of cells in the neuromuscular system can be selectively transduced by viral vectors.

Here we test the hypothesis that local upregulation of mRNA contributes to this accumulation. In muscles denervated for 1 week, both Na V 1. Neither denervation nor stimulation had any significant effect on the level or distribution of Na V 1. In addition, the expression of Na V 1. At mammalian neuromuscular junctions NMJs , innervation induces and maintains the metabolic stability of acetylcholine receptors AChRs.

To explore whether neural agrin may cause similar receptor stabilization, we injected neural agrin cDNA of increasing transfection efficiencies into denervated adult rat soleus SOL muscles. As the efficiency increased, the amount of recombinant neural agrin expressed in the muscles also increased. This agrin aggregated AChRs on muscle fibers, whose half-life increased in a dose-dependent way from 1 to 10 days.

Electrical muscle stimulation enhanced the stability of AChRs with short half-lives. Therefore, neural agrin can stabilize aggregated AChRs in a concentration- and activity-dependent way. However, there was no effect of stimulation on AChRs with a long half-life 10 days. Thus, at sufficiently high concentrations, neural agrin alone can stabilize AChRs to levels characteristic of innervated NMJs.

In innervated skeletal muscle fibers, dystrophin and beta-dystroglycan form rib-like structures costameres that appear as predominantly transverse stripes over Z and M lines. Here, we show that the orientation of these stripes becomes longitudinal in denervated muscles and transverse again in denervated electrically stimulated muscles. Skeletal muscle fibers express nonneural muscle agrin whose function is not well understood.

At lower concentration, neural agrin induced acetylcholine receptor aggregates, which colocalized with longitudinally oriented beta-dystroglycan, dystrophin, utrophin, syntrophin, rapsyn, and beta 2-laminin in denervated unstimulated fibers and with the same but transversely oriented proteins in innervated or denervated stimulated fibers. Aggregation of acetylcholine receptors AChRs in muscle fibers by nerve-derived agrin plays a key role in the formation of neuromuscular junctions.

So far, the effects of agrin on muscle fibers have been studied in culture systems, transgenic animals, and in animals injected with agrin--cDNA constructs. We have applied purified recombinant chick neural and muscle agrin to rat soleus muscle in vivo and obtained the following results. Both neural and muscle agrin bind uniformly to the surface of innervated and denervated muscle fibers along their entire length.

Muscle agrin does not cluster AChRs and at 10 times the concentration of neural agrin does not reduce binding or AChR-aggregating activity of neural agrin. Electrical muscle activity affects the stability of agrin binding and the number, size, and spatial distribution of the neural agrin--induced AChR aggregates. Injected agrin is recovered from the muscles together with laminin and both proteins coimmunoprecipitate, indicating that agrin binds to laminin in vivo.

Thus, the present approach provides a novel, simple, and efficient method for studying the effects of agrin on muscle under controlled conditions in vivo. To identify intracellular signalling pathways that transduce muscle electrical activity, we have investigated the Protein Kinase A PKA pathway in fast and slow skeletal muscle. These results were confirmed by Western blot analysis using antibodies directed against the catalytic or regulatory subunits of PKA.

PKA subunits were concentrated at the neuromuscular junction in innervated and denervated muscle fibers demonstrating that PKA is expressed post- synaptically. In addition, we also detected PKA subunits outside the junctional area, suggesting that PKA functions outside of the synaptic regions. These observations demonstrate that PKA levels in skeletal muscle are subject to control at several levels and suggest that some of the differences may be in the pattern of electrical activity that motoneurons impose on the SOL and EDL.

The Golgi complex of skeletal muscle fibers is made of thousands of dispersed elements. The distributions of these elements and of the microtubules they associate with differ in fast compared with slow and in innervated compared with denervated fibers. To investigate the role of muscle impulse activity, we denervated fast extensor digitorum longus EDL and slow soleus SOL muscles of adult rats and stimulated them directly with patterns that resemble the impulse patterns of normal fast EDL 25 pulses at Hz every 15 min and slow SOL pulses at 20 Hz every 30 sec motor units.

After 2 weeks of denervation plus stimulation, peripheral and central regions of muscle fibers were examined by immunofluorescence microscopy with regard to density and distribution of Golgi complex, microtubules, glucose transporter GLUT4, centrosomes, and endoplasmic reticulum exit sites. Slow pattern stimulation had converse effects such as a 2.

In junctional regions, where fast and slow fibers are similar, both stimulation patterns prevented a denervation-induced accumulation of GLUT4. The results indicate that patterns of muscle impulse activity, as normally imposed by motor neurons, play a major role in regulating the organization of Golgi complex and related proteins in the extrajunctional region of muscle fibers.

Nerve activity can induce long-lasting, transcription-dependent changes in skeletal muscle fibers and thus affect muscle growth and fiber-type specificity. Calcineurin signaling has been implicated in the transcriptional regulation of slow muscle fiber genes in culture, but the functional role of calcineurin in vivo has not been unambiguously demonstrated.

In contrast, calcineurin inhibitors do not block the increase in fiber size induced by nerve activity in regenerating muscle. The activation of MyHC-slow induced by direct electrostimulation of denervated regenerating muscle with a continuous low frequency impulse pattern is blocked by CsA, showing that calcineurin function in muscle fibers and not in motor neurons is responsible for nerve-dependent specification of slow muscle fibers.

Gene expression in skeletal muscle is regulated by the firing pattern of motor neurons, but the signalling systems involved in excitation- transcription coupling are unknown. Here, using in vivo transfection in regenerating muscle, we show that constitutively active Ras and a Ras mutant that selectively activates the MAPK ERK pathway are able to mimic the effects of slow motor neurons on expression of myosin genes.

Conversely, the effect of slow motor neurons is inhibited by a dominant- negative Ras mutant. These results indicate that Ras-MAPK signalling is involved in promoting nerve-activity-dependent differentiation of slow muscle fibres in vivo. To study gene expression in differentiated adult motoneuron subtypes, we used fluorescent dextrans for both anterograde and retrograde axonal tracing in adult rat and mouse.

Application of these dyes to the cut distal and proximal ends of small extramuscular nerve branches revealed both the peripheral ramifications and the cell bodies of subsets of motoneurons. We show that the soleus muscle is innervated by two nerve branches, one of which contains gamma motor and sensory axons but no alpha motor axons. By retrograde tracing of this branch, we selectively labelled gamma motoneurons.

In adult rat, the nerves innervating the soleus and extensor digitorum longus muscles contain almost exclusively axons innervating slow type I and fast type 2 muscle fibres, respectively. We selectively labelled slow and fast type motoneurons by retrograde tracing of these nerves. With immunocytochemistry we show that adult motoneurons express several homeodomain genes that are associated with motoneuron differentiation during early embryonic development.

Combining selective retrograde labelling with immunocytochemistry we compared the expression patterns in alpha and gamma motoneurons.

Terje lomo biography template

The homeodomain transcription factors Islet 1 and HB9 were expressed in slow and fast alpha motoneurons and in soleus gamma motoneurons. This biographical article about a Norwegian academic is a stub. You can help Wikipedia by expanding it. Contents move to sidebar hide. Article Talk. Read Edit View history. Tools Tools. Download as PDF Printable version.

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