The Effect And Mechanism Of Serotonin On Amyotrophic Lateral Sclerosis

Objective:5-hydroxytryptamine(5-HT),also known as serotonin,is an inhibitory neurotransmitter,but it can excite motor neurons.Amyotrophy lateral sclerosis(ALS)is a motor neuron disease.Studies have confirmed that the pathogenesis of ALS is related to 5-HT,but the effect and mechanism of 5-HT on ALS are still unclear.In order to clarify the effect of serotonin on ALS,this experiment used three serotonin receptor antagonists Granisetron,Piboserod,and Ritanserin to study its effect on the course of ALS and the changes of ALS-related pathogenic proteins TDP-43 and SOD1 G93 A.Methods:We use PCR technology to detect and screen SOD1*G93A transgenic(TG)mice that meet the requirements.From the age of 70 days onwards,Granisetron,Piboserod,and Ritanserin were continuously administered for 60 days,and the body weight,the ALSTDI score and the hanging wire test of the mice were observed or evaluated at the same time every 3 days until the ALS mice the the ALSTDI score was 4.Then,the spinal cord tissue was taken and the ALSTDI score 4 was used as the date of death to record the survival life of ALS mice.The isolated spinal cord was subjected to immunofluorescence staining to detect the changes of 5-HT and TDP-43 in the spinal cord,and Western blotting to detect the changes of TDP-43 and SOD1 G93 A in the spinal cord.Results:1.Immunofluorescence showed that the spinal cord 5-HT of TG mice was reduced compared with wild-type(WT)mice.2.The body weight of the TG mice after the intervention of Granisetron on 106 days,109 days,112 days,115 days,118 days,and 121 days was significantly lower than that of the TG control mice.There was no significant change in body weight between TG mice and TG control mice after the intervention of Piboserod and Ritanserin.The body weight of WT mice after the intervention of Granisetron,Piboserod,and Ritanserin did not change significantly compared with the WT control mice.3.The hanging wire test showed that there was no statistical difference between the TG mice in the Granisetron intervention group and the mice in the positive control group.There was a statistical difference between the TG mice in the Piboserod intervention group and the mice in the positive control group on day 97 to 127.The TG mice in the Ritanserin intervention group and the mice in the positive control group had statistically different results in the 121 day.4.There was no statistical difference between the time for the onset of disease and the ALSTDI score of 2 points,3 points,and 4 points in the TG mice in the Granisetron,Piboserod,and Ritanserin intervention groups and the positive control group.5.There was no significant difference in the survival life of TG mice between the Granisetron,Piboserod,and Ritanserin intervention groups and the positive control mice.6.Immunofluorescence results showed that the distribution of TDP-43 in the spinal cord of TG mice was higher than that of WT mice.The distribution of TDP-43 in TG mice after the intervention of Granisetron,Piposerod,and Ritanserin were all higher than that in the positive control group.7.Western blot results showed that the expressions of SOD1 G93 A and TDP43 in TG mice were increased after the intervention of Granisetron,Piboserod,and Ritanserin compared with the TG control mice.Conclusions:In our research,it was found that 5-HT is related to ALS.The use of three different 5-HT receptor antagonists(Granisetron,Piboserod,and Ritanserin)maybe affect the progression of ALS disease,and cause the ALS-related pathogenic protein SOD1 G93 A,TDP43 expression increased.