In the present review a large amount of experimental and clinical studies on ALS are discussed in an effort to dissect common pathogenic mechanisms which may provide novel information and potential therapeutic strategies for motor neuron degeneration.Protein clearing systems play a critical role in motor neuron survival during excitotoxic stress, aging and neurodegenerative disorders. Among var...

Spinal motor neurons undergo great changes in morphology, electrophysiology and molecular composition during development. Some of this maturation occurs postnatally when limbs are employed for locomotion, suggesting that neuronal activity may influence motor neuron development. To identify features of motor neurons that might be regulated by activity we first examined the structural development...

The potential of MUNE as a unique electrophysiological tool to detect early motor unit abnormalities during a clinically silent period was investigated in the plasma membrane calcium ATPase 2 (PMCA2)-heterozygous mice. There was a significant reduction in MUNE in the PMCA2-heterozygous mice as compared to the wild type littermates at two months of age. In contrast, the compound motor action pot...

During spinal cord development, ventral neural progenitor cells that express the transcription factors Olig1 and Olig2, called pMN progenitors, produce motor neurons and then oligodendrocytes. Whether motor neurons and oligodendrocytes arise from common or distinct progenitors in vivo is not known. Using zebrafish, we found that motor neurons and oligodendrocytes are produced sequentially by di...

Neurofilaments (NFs) are the major intermediate filaments in most mature neurons. Genetic approaches have now proven that NFs are an essential determinant for radial growth of axons. NF phosphorylation most probably plays an important role in this function. Further, forced over-expression of NF subunits in transgenic mice yields NF misaccumulation in motor neurons and, subsequently, causes moto...

In mammals, increased Notch signaling is held partly responsible for a lack of neurogenesis after a spinal injury. However, this is difficult to test in an essentially nonregenerating system. We show that in adult zebrafish, which exhibit lesion-induced neurogenesis, e.g., of motor neurons, the Notch pathway is also reactivated. Although apparently compatible with neuronal regeneration in zebra...

All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanisti...

Primary impairments of developmental coordination disorder (DCD) include impairments in motor skill, motor learning, and imitation. Such difficulties present challenges for individuals with DCD and may persist into adulthood, negatively impacting daily life in school, work, and social domains. A better understanding of the neural correlates of motor and imitation impairments in DCD holds the po...

The regulation of motor patterns by higher-order neuronal centers ensures appropriate motor function and behavior, but only a few studies have characterized this regulation at the cellular level. Here, we address motor pattern regulation in the stomatogastric nervous system (STNS) of the crab Cancer pagurus. This easily accessible model system is an extension of the central nervous system and c...

BACKGROUND AND PURPOSE Diagnostic confidence in motor neuron disease may be improved by the use of advanced MR imaging techniques. Our aim was to assess the accuracy (sensitivity/specificity) and agreement of combined (1)H-MR spectroscopy (proton MR spectroscopy) and diffusion tensor imaging (DTI) at 3T in patients with suspected motor neuron disease regarding detection of upper motor neuron (U...