HnRNP G Reduces Neuron Death in Amyotrophic Lateral Sclerosis by Preventing Abnormal TDP-43 Accumulation

Abstract Background: Heterologous ribonucleoprotein (hnRNP) G protein was found to significantly down-regulate in the spinal cord of amyotrophic lateral sclerosis (ALS) mouse model in our previous study, but the down-regulated effects of hnRNP G in ALS haven’t been known up to now. Therefore, we further studied the possible effects of hnRNP G on the spinal neuron death in TG(SOD1*G93A)1Gur (TG) mice. Methods: Eighteen TG mice and eighteen SOD1 wild-type (WT) mice were divided into 6 groups. The hnRNP G of spinal cord were analyzed using immunofluorescent histochemistry and Western blot. Three hnRNP G-siRNA were transfected into PC12 cells and observed the alteration of proliferation rate and intracellular proteins after gene silenced using the CCK8 and Western blot. Results: Here, we reported that the distribution of hnRNP G positive cells in the posterior horn was more than that in the central canal and its surrounding gray matter more than that in the anterior horn. hnRNP G protein expressed in neurons. hnRNP G expression in the cervical and thoracic segments of TG mice in pre-onset group was significantly higher than that in control group. hnRNP G expression in the thoracic and lumbar segments of TG mice in onset group was lower than that in control group. hnRNP G expression in the cervical and thoracic segments of TG mice in progressive group decreased, while that in the lumbar segment of TG mice in progression group significantly increased. After hnRNP G-siRNA silenced, the proliferation rate of PC12 cells was slower than that in control group, SOD1 expression didn’t significantly change, both TDP-43 and Bax expression significantly increased in PC12 cells after hnRNP G gene silenced. Conclusions: Our study revealed that the distribution of hnRNP G in the spinal cord of ALS mice showed the possible protective effect on the progression of ALS, its mechanism maybe prevent neuron death through reducing abnormal TDP-43 accumulation in the spinal cord of ALS-like mice.