title: Influences of hyperthermia-induced seizures on learning, memory and phosphorylative state of CaMKIIα in rat hippocampus.
abstract: Febrile seizure (FS) remains the most common childhood neurological emergency. Although many studies have been done, controversy exists as to whether these seizures are associated with a significant risk for cognitive impairment. The aim of our study is to check whether there is a spatial learning and memory deficit in the experimental FS rats using a heated-air FS paradigm and to determine the possible molecular mechanism of cognitive impairment. On days 10 to 12 postpartum, the male rat pups were subjected to one, three, or nine episodes of brief hyperthermia-induced seizures (HS). At adolescence and adulthood, the rats subjected to three, or nine episodes of HS had significant deficits in spatial learning and memory tested by Morris water maze. At adulthood, no apparent hippocampal neuronal loss was found in any HS group, but the seizure threshold to flurothyl was decreased significantly in the rats subjected to nine episodes of HS. In the rats subjected to three, or nine episodes of HS, the Western immunoblotting showed that there was a significant translocation of Ca(2+)-calmodulin stimulated protein kinase II (CaMKII) from the postsynaptic density to the cytosol. In the postsynaptic density the phosphorylation of CaMKIIα Thr(286) was reduced significantly, but the phosphorylation of CaMKIIα Thr(305) was increased significantly. Our study showed early-life brief but recurrent HS caused long-term cognitive impairment and CaMKIIα was involved in carrying forward the signal resulting from HS. The change of the phosphorylative level in Thr(286) and Thr(305) sites of CaMKIIα may underlie the molecular mechanism for the HS related cognitive impairment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Pediatrics, Yichang Central Hospital, Yichang, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, PR China; Department of Neonatology, Guangzhou Women and Children׳s Medical Center, Guangzhou, PR China. Electronic address: zhanglian86de@gmail.com.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D005481:Flurothyl / Q000494:pharmacology; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D006358:Hot Temperature; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009483:Neuropsychological Tests; D010766:Phosphorylation; D010812:Physical Stimulation; D057907:Post-Synaptic Density / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D003294:Seizures, Febrile / Q000473:pathology / Q000503:physiopathology*; D013028:Space Perception / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; C581829:Camk2n1 protein, rat; D002352:Carrier Proteins; D003292:Convulsants; D005481:Flurothyl
keywords: CaMKII; Hyperthermia-induced seizure; Learning and memory; Phosphorylation; Postsynaptic density