Quantitative Axon Terminal and End-plate Morphology in Amyotrophic Lateral Sclerosis

Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice

“…This is similar to the reinnervation of muscle fibers described previously in ALS patients (28). Here, we demonstrate that denervation-induced sprouting at NMJ modifies the uptake properties of motoneurons in symptomatic ALS mice such that uptake of adenoviruses and resulting motoneuron retrograde transduction is increased after i.m.…”

Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice

“…This is similar to the reinnervation of muscle fibers described previously in ALS patients (28). Here, we demonstrate that denervation-induced sprouting at NMJ modifies the uptake properties of motoneurons in symptomatic ALS mice such that uptake of adenoviruses and resulting motoneuron retrograde transduction is increased after i.m.…”

Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

“…The level of denervation did not appear to progress between pre‐symptomatic and late‐symptomatic stages, despite an obviously worsened phenotype in the mice. This is likely due to reinnervation, which occurs during disease progression (Bjornskov et al, ; Frey et al, ; Fischer et al, ; Schaefer et al, ), and is reflected in the increase in partially occupied endplates seen in this muscle group in our study.…”

Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS

“…5i ). IGF-2 can induce motor nerve sprouting 35 and some motor neurons show a great capacity for sprouting and regeneration in the SOD1 G93A mouse 36 37 38 39 40 . Therefore we next investigated if our IGF-2 treatment had induced regeneration in the lumbrical muscles in the hind paws of treated mice.…”

“…In our culture system, the addition of IGF-2 to the media could be seen as mimicking such muscle-secretion of a motor neuron survival factor rather than demonstrating a cell intrinsic survival factor. Nonetheless, this implies that it could be sufficient to deliver IGF-2 to muscle, without retrograde delivery, to protect motor neurons that are still connected with muscle or within close enough range to benefit from secreted IGF-2, especially as motor neurons show regenerative capacity also in ALS patients 40 . However, it is likely more beneficial to deliver IGF-2 also to motor neurons, through retrograde delivery, as in our in vivo approach, or through direct injection into spinal cord to target motor neurons that have retracted further from the muscle.…”

Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice

“…This is similar to the reinnervation of muscle fibers described previously in ALS patients (28). Here, we demonstrate that denervation-induced sprouting at NMJ modifies the uptake properties of motoneurons in symptomatic ALS mice such that uptake of adenoviruses and resulting motoneuron retrograde transduction is increased after i.m.…”

Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

“…The level of denervation did not appear to progress between pre‐symptomatic and late‐symptomatic stages, despite an obviously worsened phenotype in the mice. This is likely due to reinnervation, which occurs during disease progression (Bjornskov et al, ; Frey et al, ; Fischer et al, ; Schaefer et al, ), and is reflected in the increase in partially occupied endplates seen in this muscle group in our study.…”

Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS

“…5i ). IGF-2 can induce motor nerve sprouting 35 and some motor neurons show a great capacity for sprouting and regeneration in the SOD1 G93A mouse 36 37 38 39 40 . Therefore we next investigated if our IGF-2 treatment had induced regeneration in the lumbrical muscles in the hind paws of treated mice.…”

“…In our culture system, the addition of IGF-2 to the media could be seen as mimicking such muscle-secretion of a motor neuron survival factor rather than demonstrating a cell intrinsic survival factor. Nonetheless, this implies that it could be sufficient to deliver IGF-2 to muscle, without retrograde delivery, to protect motor neurons that are still connected with muscle or within close enough range to benefit from secreted IGF-2, especially as motor neurons show regenerative capacity also in ALS patients 40 . However, it is likely more beneficial to deliver IGF-2 also to motor neurons, through retrograde delivery, as in our in vivo approach, or through direct injection into spinal cord to target motor neurons that have retracted further from the muscle.…”

Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice

“…This is similar to the reinnervation of muscle fibers described previously in ALS patients (28). Here, we demonstrate that denervation-induced sprouting at NMJ modifies the uptake properties of motoneurons in symptomatic ALS mice such that uptake of adenoviruses and resulting motoneuron retrograde transduction is increased after i.m.…”

Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

“…The level of denervation did not appear to progress between pre‐symptomatic and late‐symptomatic stages, despite an obviously worsened phenotype in the mice. This is likely due to reinnervation, which occurs during disease progression (Bjornskov et al, ; Frey et al, ; Fischer et al, ; Schaefer et al, ), and is reflected in the increase in partially occupied endplates seen in this muscle group in our study.…”

Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS

“…5i ). IGF-2 can induce motor nerve sprouting 35 and some motor neurons show a great capacity for sprouting and regeneration in the SOD1 G93A mouse 36 37 38 39 40 . Therefore we next investigated if our IGF-2 treatment had induced regeneration in the lumbrical muscles in the hind paws of treated mice.…”

“…In our culture system, the addition of IGF-2 to the media could be seen as mimicking such muscle-secretion of a motor neuron survival factor rather than demonstrating a cell intrinsic survival factor. Nonetheless, this implies that it could be sufficient to deliver IGF-2 to muscle, without retrograde delivery, to protect motor neurons that are still connected with muscle or within close enough range to benefit from secreted IGF-2, especially as motor neurons show regenerative capacity also in ALS patients 40 . However, it is likely more beneficial to deliver IGF-2 also to motor neurons, through retrograde delivery, as in our in vivo approach, or through direct injection into spinal cord to target motor neurons that have retracted further from the muscle.…”