title: Prenatal melamine exposure impairs spatial cognition and hippocampal synaptic plasticity by presynaptic and postsynaptic inhibition of glutamatergic transmission in adolescent offspring.
abstract: Our previous studies showed that prenatal melamine exposure (PME) could impair spatial cognition and hippocampal long-term potentiation (LTP). More importantly, the synaptic dysfunction induced by PME was associated with the probability of presynaptic glutamate release. Considering the crucial role of the other form of synaptic plasticity, long-term depression (LTD), in some types of learning and memory process, the aim of present study was to investigate if the hippocampal LTD and cognitive flexibility were affected. And then we attempted to explore the underlying mechanism. The animal model was produced by melamine exposure throughout gestational period with 400mg/kg bodyweight, the male offspring rats were used in the study. Morris water maze (MWM) test was performed, and then LTD was recorded from Schaffer collaterals to CA1 region in the hippocampus. Behavioral test showed that learning, reference memory and re-acquisition learning abilities were impaired significantly by PME. The field excitatory postsynaptic potentials (fEPSPs) slopes of LTD were significantly higher after PME. Furthermore, the data of whole-cell patch-clamp experiments showed that PME markedly diminished the frequencies of spontaneous EPSCs (sEPSCs) and simultaneously reduced the amplitude of sEPSCs. In conclusion, PME inhibited glutamate transmission presynaptically and postsynaptically which could contribute importantly to the depressed hippocampal synaptic plasticity and further induced cognitive deficits in MWM tests.
authors.affiliation: South China Research Center for Acupuncture & Moxibustion, Guangzhou University of Chinese Medicine, 510006 Guangzhou, China; Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, 510006 Guangzhou, China; Department of Physiology, University of Saskatchewan, S7N 5E5 Saskatoon, Canada. Electronic address: al_totti@sina.com.
authors.forename: Lei
authors.initials: L
authors.lastname: An
authors.affiliation: South China Research Center for Acupuncture & Moxibustion, Guangzhou University of Chinese Medicine, 510006 Guangzhou, China; Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, 510006 Guangzhou, China. Electronic address: mercury1984@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000175:diagnosis; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000175:diagnosis*; D051381:Rats; D017208:Rats, Wistar; D065853:Spatial Learning / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D014227:Triazines / Q000633:toxicity*
chemical_list: D014227:Triazines; D018698:Glutamic Acid; C011907:melamine
keywords: Cognitive flexibility; Hippocampus; Long-term depression; Melamine; Synaptic transmission