{"title":"抑制AMPA受体的内吞作用可通过淀粉样β神经毒性中的c-Fos/BDNF信号转导减轻认知缺陷","authors":"Kimia Eyvani, Negin Letafatkar, Parvin Babaei","doi":"10.1080/0361073X.2024.2377440","DOIUrl":null,"url":null,"abstract":"<p><p>Glutamatergic imbalance, particularly downregulation of <i>α</i>-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid receptor (AMPARs) endocytosis, has been addressed as a possible reason for cognitive dysfunctions in Alzheimer's disease (AD). We hypothesized that inhibition of AMPAR endocytosis may ameliorate memory impairment in AD model of rats. To approach this, twenty-four adults male Wistar rats were divided into three groups: saline + saline (control group), A<i>β</i> + saline, and A<i>β</i> + Tat-GluR23Y (AMPA endocytosis inhibitor). Animals received an intracerebroventricular (i.c.v) injection of A<i>β</i> (1-42) to induce neuro-toxicity, followed by chronic administration of GluR23Y, and further behavioral assessments by MWM. Afterward, the hippocampal level of Brain Derived Neurotrophic Factor (BDNF) and c-Fos was measured via Western blotting. The results of our study revealed that chronic administration of GluR23Y improved both working and reference memories evidenced by shorter latency time and longer total time spent in the target zone in MWM. Additionally, this improvement was paralleled by an increase in BDNF, but a decrease in c-Fos. In conclusion, GluR23Y improves spatial memory impairment at least partly via elevating neuroprotective factor of BDNF and reducing apoptotic protein of c-Fos.</p>","PeriodicalId":12240,"journal":{"name":"Experimental Aging Research","volume":" ","pages":"1-13"},"PeriodicalIF":1.4000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"AMPA Receptors Endocytosis Inhibition Attenuates Cognition Deficit Via c-Fos/BDNF Signaling in Amyloid <i>β</i> Neurotoxicity.\",\"authors\":\"Kimia Eyvani, Negin Letafatkar, Parvin Babaei\",\"doi\":\"10.1080/0361073X.2024.2377440\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Glutamatergic imbalance, particularly downregulation of <i>α</i>-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid receptor (AMPARs) endocytosis, has been addressed as a possible reason for cognitive dysfunctions in Alzheimer's disease (AD). We hypothesized that inhibition of AMPAR endocytosis may ameliorate memory impairment in AD model of rats. To approach this, twenty-four adults male Wistar rats were divided into three groups: saline + saline (control group), A<i>β</i> + saline, and A<i>β</i> + Tat-GluR23Y (AMPA endocytosis inhibitor). Animals received an intracerebroventricular (i.c.v) injection of A<i>β</i> (1-42) to induce neuro-toxicity, followed by chronic administration of GluR23Y, and further behavioral assessments by MWM. Afterward, the hippocampal level of Brain Derived Neurotrophic Factor (BDNF) and c-Fos was measured via Western blotting. The results of our study revealed that chronic administration of GluR23Y improved both working and reference memories evidenced by shorter latency time and longer total time spent in the target zone in MWM. Additionally, this improvement was paralleled by an increase in BDNF, but a decrease in c-Fos. In conclusion, GluR23Y improves spatial memory impairment at least partly via elevating neuroprotective factor of BDNF and reducing apoptotic protein of c-Fos.</p>\",\"PeriodicalId\":12240,\"journal\":{\"name\":\"Experimental Aging Research\",\"volume\":\" \",\"pages\":\"1-13\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Aging Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/0361073X.2024.2377440\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Aging Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/0361073X.2024.2377440","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
AMPA Receptors Endocytosis Inhibition Attenuates Cognition Deficit Via c-Fos/BDNF Signaling in Amyloid β Neurotoxicity.
Glutamatergic imbalance, particularly downregulation of α-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid receptor (AMPARs) endocytosis, has been addressed as a possible reason for cognitive dysfunctions in Alzheimer's disease (AD). We hypothesized that inhibition of AMPAR endocytosis may ameliorate memory impairment in AD model of rats. To approach this, twenty-four adults male Wistar rats were divided into three groups: saline + saline (control group), Aβ + saline, and Aβ + Tat-GluR23Y (AMPA endocytosis inhibitor). Animals received an intracerebroventricular (i.c.v) injection of Aβ (1-42) to induce neuro-toxicity, followed by chronic administration of GluR23Y, and further behavioral assessments by MWM. Afterward, the hippocampal level of Brain Derived Neurotrophic Factor (BDNF) and c-Fos was measured via Western blotting. The results of our study revealed that chronic administration of GluR23Y improved both working and reference memories evidenced by shorter latency time and longer total time spent in the target zone in MWM. Additionally, this improvement was paralleled by an increase in BDNF, but a decrease in c-Fos. In conclusion, GluR23Y improves spatial memory impairment at least partly via elevating neuroprotective factor of BDNF and reducing apoptotic protein of c-Fos.
期刊介绍:
Experimental Aging Research is a life span developmental and aging journal dealing with research on the aging process from a psychological and psychobiological perspective. It meets the need for a scholarly journal with refereed scientific papers dealing with age differences and age changes at any point in the adult life span. Areas of major focus include experimental psychology, neuropsychology, psychobiology, work research, ergonomics, and behavioral medicine. Original research, book reviews, monographs, and papers covering special topics are published.