Structural Charactaristics Of Neuromuscular Junction In Familial ALS

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease that can cause motor neuron degeneration in the spinal cord and motor cortex.Although most cases of ALS are sporadic,copper-zinc superoxide dismutase-1(SOD1)mutations are responsible for 10%-20% of familial ALS.Current treatment methods are not effective and a large part of them are damaged The function cannot be restored at all,or only partially restored,and other treatments are usually required during the life cycle of the patient.Studies have shown that intervention strategies based on different stages can effectively prevent and control familial ALS.Although there are indeed some improvements to this degenerative disease However,even with the continuous advancement of modern medicine and science,the exact pathogenesis is still unclear.This study used the WT&SOD1G93A mouse model from 40 days to120 days to study the structure of the neuromuscular junction of SOD1 mice.The experimental results showed that in 40-day-old mice,90% of WT&SODI mice had no degeneration in the neuromuscular junction structure;in60-day-old mice,there was no slight degeneration;and in 90-day-old mice,No severe degeneration occurred,but in 120-day-old mice,there was severe structural distortion and paralysis.Objective: To observe the structural characteristics of familial ALS neuromuscular junctions in different age groups.Method: From male hemizygous carriers(B6SJL-Tg(SOD1-G93A)1Gur/J)and female B6SJL/F1 hybrids,female G93ASOD1 transgenic mice and age-matched wild-type(WT littermate partners,both All were purchased from Jackson)laboratory.The animals were kept in an environment with controlled humidity and temperature,and 12:12h light was performed in a dark schedule,and sterile rodent food and sterile food were provided without specific pathogens.Result:1.The following results show that both WT and SOD1 are present in40-day-old mice.Inside the Tibialis anterior of G93ASOD1 mice(TA)and gastrocnemius(GN)construction.The picture(above)shows the number of neuromuscular junctions(NMJ)in various gatherings.The neurofilament heavy polypeptide(tubulin,green)points to the presynaptic end.α-Bungarotoxins(BTX,white)mark the postsynaptic space,and synaptophysin(p38-1,red)is used for synaptic vesicles.The following results show that neither of them has degraded and is 90% complete.2.It shows WT and SOD1 in 60-day-old mice.The design of the Tibialis anterior(TA)and gastrocnemius(GN)of G93ASOD1 mice.The representative picture(top)shows the number of neuromuscular intersections in various gatherings.Neurofilament heavy polypeptide(tubulin,green)points to the presynaptic end.α-Bungarotoxins(BTX,white)marks the postsynaptic area,and synaptophysin(p38-1,red)is used for synaptic vesicles.The results show that in both WT and SOD1,the denaturation is about 70% to 80%,which means that a slight denaturation has occurred.3.Both WT and SOD1 were shown in 90-day-old mice.The structure of the Tibialis anterior(TA)and gastrocnemius(GN)muscles in G93ASOD1 mice.A representative image(above)shows the number of neuromuscular junctions(NMJ)in different groups.The neurofilament heavy polypeptide(tubulin,green)represents the presynaptic end.The α-Bungarotoxins(BTX,white)that marks the postsynaptic domain,synaptic vesicles(p38-1,red)is used for synaptic vesicles.Data from WT and SOD1 show that in 90-day-old mice,degeneration is not serious,about 60% to 70%.4.Both WT and SOD1 were displayed in mice at 120 days.The structure of the Tibialis anterior(TA)and gastrocnemius(GN)muscles in G93ASOD1 mice.Representative images(top)show the number of neuromuscular junctions(NMJ)in different groups.The neurofilament heavy polypeptide(tubulin,green)represents the presynaptic end.α-Bungarotoxins labeled postsynaptic domain.Conclusion:In this study,after observing the structural characteristics of the neuromuscular junction in WT and SOD1 mice at 40,60,90 and 120 days,we concluded that at 40 days,NMJ innervation has appeared Disappearance,loss of motor axons,and huge structural damage to the NMJ at 60 and 90 days.Based on our data,we observed structural changes in presynaptic and postsynaptic structures and a gradual decrease in synaptic vesicles.Further research is needed to explore the complex system phenotype of ALS.In this study,we have identified the basic molecular events of these systemic changes and provided experimental evidence for their feasibility as a drug target.