Rui Sun, Kedi Xi, Shengjun Ji, Xing Song, Dan Xi, Wenming Yin, Yingjie Shao, Wendong Gu, Jingting Jiang
{"title":"TDP-43 参与了辐射诱导的神经元损伤,但可能不是通过 BDNF/TrkB 途径。","authors":"Rui Sun, Kedi Xi, Shengjun Ji, Xing Song, Dan Xi, Wenming Yin, Yingjie Shao, Wendong Gu, Jingting Jiang","doi":"10.1667/RADE-23-00168.1","DOIUrl":null,"url":null,"abstract":"<p><p>Cognitive dysfunction is the most common form of radiation-induced brain injury. TDP-43 is known to be associated with hippocampal degeneration and cognitive dysfunction, in this study we wanted to know if it also had an effect on radiation-induced hippocampus damage. At first, we found the expression of TDP-43 and p-TDP-43 was increased in the hippocampus of rats with radiation-induced cognitive dysfunction. Single-cell RNA-seq analysis of the rat hippocampus showed that TDP-43 was expressed in all cell types and was significantly upregulated in neuron cells after irradiation. Enrichment analysis of gene ontology (GO) functions and KEGG pathways showed that the differential expression genes in neuron after irradiation may be involved in synaptic plasticity. In vitro, the expression of TDP-43 was also increased in neuron cells after irradiation, while the expression of brain-derived neurotrophic factor (BDNF), TrkB, typical synaptic signature proteins (SYN, GAP43 and PSD95), β-tubulin and dendritic spines were decreased. In the irradiated neurons, the β-tubulin, dendritic and spines typical synaptic signature proteins had more severe damage in pcDNA3.1-TDP-43 plasmid transfections group, however, the damages were alleviated in the siRNA-TDP-43 plasmid transfections group. BDNF was highly expressed in the irradiated pcDNA3.1-TDP-43 plasmid transfections group, while its expression was decreased in the siRNA-TDP-43 group. The TrkB expression was significantly reduced in neurons after exposure to ionizing radiation, however, there was no significant correlation with TDP-43 expression. These data indicate that TDP-43 is involved in radiation-induced neuronal synaptic plasticity decline and developmental damage, furthermore, the BDNF/TrkB signaling pathway may not be involved in this process.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"TDP-43 was Involved in Radiation-induced Neuronal Damage and May Not Through the BDNF/TrkB Pathway.\",\"authors\":\"Rui Sun, Kedi Xi, Shengjun Ji, Xing Song, Dan Xi, Wenming Yin, Yingjie Shao, Wendong Gu, Jingting Jiang\",\"doi\":\"10.1667/RADE-23-00168.1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cognitive dysfunction is the most common form of radiation-induced brain injury. TDP-43 is known to be associated with hippocampal degeneration and cognitive dysfunction, in this study we wanted to know if it also had an effect on radiation-induced hippocampus damage. At first, we found the expression of TDP-43 and p-TDP-43 was increased in the hippocampus of rats with radiation-induced cognitive dysfunction. Single-cell RNA-seq analysis of the rat hippocampus showed that TDP-43 was expressed in all cell types and was significantly upregulated in neuron cells after irradiation. Enrichment analysis of gene ontology (GO) functions and KEGG pathways showed that the differential expression genes in neuron after irradiation may be involved in synaptic plasticity. In vitro, the expression of TDP-43 was also increased in neuron cells after irradiation, while the expression of brain-derived neurotrophic factor (BDNF), TrkB, typical synaptic signature proteins (SYN, GAP43 and PSD95), β-tubulin and dendritic spines were decreased. In the irradiated neurons, the β-tubulin, dendritic and spines typical synaptic signature proteins had more severe damage in pcDNA3.1-TDP-43 plasmid transfections group, however, the damages were alleviated in the siRNA-TDP-43 plasmid transfections group. BDNF was highly expressed in the irradiated pcDNA3.1-TDP-43 plasmid transfections group, while its expression was decreased in the siRNA-TDP-43 group. The TrkB expression was significantly reduced in neurons after exposure to ionizing radiation, however, there was no significant correlation with TDP-43 expression. 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TDP-43 was Involved in Radiation-induced Neuronal Damage and May Not Through the BDNF/TrkB Pathway.
Cognitive dysfunction is the most common form of radiation-induced brain injury. TDP-43 is known to be associated with hippocampal degeneration and cognitive dysfunction, in this study we wanted to know if it also had an effect on radiation-induced hippocampus damage. At first, we found the expression of TDP-43 and p-TDP-43 was increased in the hippocampus of rats with radiation-induced cognitive dysfunction. Single-cell RNA-seq analysis of the rat hippocampus showed that TDP-43 was expressed in all cell types and was significantly upregulated in neuron cells after irradiation. Enrichment analysis of gene ontology (GO) functions and KEGG pathways showed that the differential expression genes in neuron after irradiation may be involved in synaptic plasticity. In vitro, the expression of TDP-43 was also increased in neuron cells after irradiation, while the expression of brain-derived neurotrophic factor (BDNF), TrkB, typical synaptic signature proteins (SYN, GAP43 and PSD95), β-tubulin and dendritic spines were decreased. In the irradiated neurons, the β-tubulin, dendritic and spines typical synaptic signature proteins had more severe damage in pcDNA3.1-TDP-43 plasmid transfections group, however, the damages were alleviated in the siRNA-TDP-43 plasmid transfections group. BDNF was highly expressed in the irradiated pcDNA3.1-TDP-43 plasmid transfections group, while its expression was decreased in the siRNA-TDP-43 group. The TrkB expression was significantly reduced in neurons after exposure to ionizing radiation, however, there was no significant correlation with TDP-43 expression. These data indicate that TDP-43 is involved in radiation-induced neuronal synaptic plasticity decline and developmental damage, furthermore, the BDNF/TrkB signaling pathway may not be involved in this process.
期刊介绍:
Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology
and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically
ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or
biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with
chemical agents contributing to the understanding of radiation effects.