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

doi:10.3969/j.issn.1004-616x.2026.01.005

Abstract

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： STX exposure from gestation and lactation to adulthood induces cognitive impairment in F1 generation mice，and its mechanism of action may involve the oxidative phosphorylation pathway.

Key words: saxitoxin, cognitive impairment, proteomics, oxidative phosphorylation

CLC Number:

R996.3

CHEN Mei, HUANG Haiyan, LIN Lingling, REN Xiaohu, CHEN Xiao, LIU Yungang, LIU Jianjun. Effect and mechanism of saxitoxin exposure on cognitive function in F1 generation mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2026, 38(1): 27-33.

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Effect and mechanism of saxitoxin exposure on cognitive function in F1 generation mice

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