癌变·畸变·突变2026，Vol.38Issue(1)：27-33,7.DOI:10.3969/j.issn.1004-616x.2026.01.005
石房蛤毒素暴露对F1代小鼠认知功能的影响及其作用机制
Effect and mechanism of saxitoxin exposure on cognitive function in F1 generation mice
摘要
Abstract
OBJECTIVE:To investigate effects of saxitoxin(STX)exposure on cognitive function in F1 generation mice and its underlying mechanisms.METHODS:C57BL/6J mice were exposed to STX via drinking water during gestation and lactation to adulthood at doses of 0.00,0.02,0.20,or 2.00 μg/kg.Cognitive and memory functions were assessed in postnatal day 60(PND60)and PND180 mice using the Morris water maze test,cortical neurotoxicity was evaluated by NeuN immunohistochemical staining,differentially expressed proteins in cortical tissues were screened and analyzed via Tandem Mass Tag(TMT)quantitative proteomics and enrichment analysis,key proteins were validated by Western blot,and cortical ATP levels were measured with a commercial kit.RESULTS:At STX doses of 0.02,0.20,and 2.00 μg/kg,no significant differences in maternal body weight,water intake,or body weight gain of F1 generation mice compared with the control group(P>0.05).In the Morris water maze,PND180 offspring exposed to STX exhibited prolonged platform-finding latency,reduced platform crossings,and decreased target quadrant occupancy compared to the control group(all P<0.05),while no differences were detected at PND60.Immunohistochemical analysis revealed significantly fewer cortical neurons in PND180 mice following STX exposure(P<0.05).Proteomic profiling identified 295 DEPs at PND60 and 327 DEPs at PND180 in the 2.00 μg/kg group.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses highlighted oxidative phosphorylation(OXPHOS)as a critical pathway in both age groups.Western blot confirmed elevated expression of OXPHOS-related proteins Ndufs1 and Ndufb9 in PND180 cortical tissues(P<0.05),with no significant changes at PND60.Cortical ATP levels were also significantly reduced in STX-exposed PND180 mice(P<0.05).CONCLUSION:STXexposure from gestation and lactation to adulthood induces cognitive impairment in F1 generation mice,and its mechanism of action may involve the oxidative phosphorylation pathway.关键词
石房蛤毒素/认知损伤/蛋白质组学/氧化磷酸化Key words
saxitoxin/cognitive impairment/proteomics/oxidative phosphorylation分类
医药卫生引用本文复制引用
陈妹,黄海燕,林玲玲,任晓虎,陈效,刘云岗,刘建军..石房蛤毒素暴露对F1代小鼠认知功能的影响及其作用机制[J].癌变·畸变·突变,2026,38(1):27-33,7.基金项目
深圳市基础研究学科布局项目(JCYJ20180508152311822) （JCYJ20180508152311822）
深圳市医学重点学科建设经费资助项目(SZXK069) （SZXK069）
深圳市医疗卫生三名工程项目(SZSM202211010) （SZSM202211010）
