BACKGROUND Hypoglossal (XII) motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity whi...

It has been shown that abnormalities in axonal transport occur in several mouse models with motoneuron degeneration and also in the human disease amyotrophic lateral sclerosis. In this report, we have examined the potential of neurotrophic factors to act on axonal transport properties in a mouse mutant, progressive motor neuronopathy (pmn). This mouse mutant has been characterized as a "dying-b...

Muscle-derived factors are known to be important for the survival of developing spinal motoneurons, but the molecules involved have not been characterized. Hepatocyte growth factor/scatter factor (HGF/SF) plays an important role in muscle development and motoneuron axon outgrowth. We show that HGF/SF has potent neurotrophic activity (EC50=2 pM) for a subpopulation (40%) of purified embryonic ra...

Members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor (LIF) gene family play an essential role for survival of developing and postnatal motoneurons. When subunits of the shared receptor complex are inactivated by homologous recombination, the mice die at approximately birth and exhibit reduced numbers of motoneurons in the spinal cord and brainstem nuclei. However, mice i...

Ciliary neurotrophic factor (CNTF) has potent survival-promoting effects on motoneurons in vitro and in vivo. We examined knockout mice with null mutations of the gene for either CNTF itself or the alpha-subunit of the CNTF receptor (CNTFRalpha) to assess whether CNTF and/or its receptors are involved in the development of a sexually dimorphic neuromuscular system. Male rodents have many more m...

Down syndrome cell adhesion molecule, Dscam, serves diverse neurodevelopmental functions, including axon guidance and synaptic adhesion, as well as self-recognition and self-avoidance, depending on the neuron type, brain region, or species under investigation. In Drosophila, the extensive molecular diversity that results from alternative splicing of Dscam1 into >38,000 isoforms provides neurons...

We compared the survival requirements of early- and late-born motoneurons from E5 chicken spinal cord. Density gradient centrifugation followed by immunopanning using SC1 antibody allowed us to purify two size classes of motoneuron. Large motoneurons retained by 6.8% metrizamide were shown by BrdU labeling in ovo to be born on average 1.5 d earlier than the small motoneurons recovered from the ...

Injury to neonatal nerves, unlike adult nerves, results in poor regeneration and extensive motoneuron death. We examined whether exposure to a more mature nerve environment could rescue axotomized motoneurons following neonatal injury. The sciatic nerve in 1 hindlimb of 3-day-old (P3) rats was transected and the cut end sutured to a nerve graft taken from donor rats, which ranged between P3 and...

Bidirectional molecular communication between the motoneuron and the muscle is vital for neuromuscular junction (NMJ) formation and maintenance. The molecular mechanisms underlying such communication are of keen interest and could provide new targets for intervention in motoneuron disease. Here, we developed a microfluidic platform with motoneuron cell bodies on one side and muscle cells on the...