Particulate matter (PM 10 ) exacerbates on MK-801-induced schizophrenia-like behaviors through the inhibition of ERK-CREB-BDNF signaling pathway
Ecotoxicology and Environmental Safety(2024)
摘要
Particulate matter (PM), released into the air by a variety of natural and human activities, is a key indicator of air pollution. Although PM is known as the extensive health hazard to affect a variety of illness, few studies have specifically investigated the effects of PM 10 exposure on schizophrenic development. In the present study, we aimed to investigate the impact of PM 10 on MK -801, N-methyl-D-aspartate (NMDA) receptor antagonist, induced schizophrenia -like behaviors in C57BL/6 mouse. Preadolescent mice were exposed PM 10 to 3.2 mg/m 3 concentration for 4 h/day for 2 weeks through a compartmentalized whole -body inhalation chamber. After PM 10 exposure, we conducted behavioral tests during adolescence and adulthood to investigate longitudinal development of schizophrenia. We found that PM 10 exacerbated schizophrenia -like behavior, such as psychomotor agitation, social interaction deficits and cognitive deficits at adulthood in MK -801 -induced schizophrenia animal model. Furthermore, the reduced expression levels of brain -derived neurotrophic factor (BDNF) and the phosphorylation of BDNF related signaling molecules, extracellular signal -regulated kinase (ERK) and cAMP response element -binding protein (CREB), were exacerbated by PM 10 exposure in the adult hippocampus of MK -801treated mice. Thus, our present study demonstrates that exposure to PM 10 in preadolescence exacerbates the cognitive impairment in animal model of schizophrenia, which are considered to be facilitated by the decreased level of BDNF through reduced ERK-CREB expression.
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关键词
Particulate matter,Schizophrenia,MK-801,Brain-derived neurotrophic factor,Extracellular signal-regulated kinase,CAMP response element-binding protein
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