Dominant spinocerebellar ataxias (SCA) are heterogeneous neurological diseases with phenotypes consisting of cerebellar ataxia, extrapyramidal signs, dysarthria, oculomotor abnormalities, motor neuron signs, cognitive decline, epilepsy, autonomic dysfunction, sensory deficits, and psychiatric manifestations.
Other groups have shown similarly that astrocyte transplantation in a rodent transgenic model of ALS expressing human SOD1*G37R attenuated motor neuron loss and motor decline.
We reported a large family with a mitochondrial myopathy associated with motor neuron disease and cognitive decline resembling frontotemporal dementia (FTD).
Previous reports on mice with hypomorphic mutations in dynein, the Cra1/+, Loa/+ or Swl/+ mice, described a late-onset degeneration of motor neurons, with progressive decline in motor neuron function and number [9], or an early-onset degeneration of proprioceptive sensory neurons.
The progressive decline of motor neuron function during aging leads to denervation of muscle fibers, which can result in muscle mass loss [ 32, 33].
Specifically, these motor neurons show a decline in excitatory postsynaptic potential, which is the electrical change that enables the nerve impulse to cross the gap (synaptic cleft) that separates one neuron in the pathway from the next.
After injection, they found that the grafted cells survived in the diseased tissues and differentiated efficiently into astrocytes, with microgliosis alleviated at the transplanted sites; additionally, survival was extended, motor neuron loss was ameliorated and declines in forelimb motor capability slowed, and respiratory functions improved [ 72].
Potential candidates mechanisms for this reduced EMG activity during the COD task include either disfacilitation of the motor neuron pool due to a progressive decline in muscle spindle responsiveness [ 51, 56], or presynaptic inhibition of Ia afferent feedback [ 57, 58].
We described a novel heterozygous CHCHD10 mutation (c.176C>T; p.Ser59Leu) in a large French family with a phenotype including cognitive decline resembling frontotemporal dementia (FTD), motor neuron disease (MND), cerebellar ataxia, and mitochondrial myopathy with multiple mtDNA deletions.
Alternatively, CMAPs may remain stable in the face of a decline in motor unit number estimation values, suggesting lower motor neuron loss with compensatory collateral re-innervation (Swoboda et al., 2005).
