title: Dizocilpine reduces head diameter of dendritic spines in the hippocampus of adolescent rats.
abstract: Cognitive deficits are the core symptoms of schizophrenia. Spine deficits have been found in hippocampus of schizophrenia patients, and were associated with cognitive impairments. N-methyl-D-asparate receptors (NMDARs) had been known to play a critical role in synaptic pruning and stabilization during adolescence. In the present study, male adolescent rats were exposed to dizocilpine (MK-801) (0.2mg/kg i.p qd) or 0.9% saline for 14 days. Then spatial memory, spine morphological changes and RhoA, Rac1, Cdc42 mRNA levels in hippocampus were measured. As a result, MK-801 impaired spatial memory in the adolescent rats, as well as reduced the proportion of mushroom spines and increased the proportion of stubby spines in hippocampus. MK-801 also reduced the expression levels of Rac1 and Cdc42 mRNA and upregulated RhoA mRNA in hippocampus. These results imply that subchronic MK-801 administration during adolescence might disturb the expression of RhoA, Rac1 and Cdc42 mRNA, and then lead to the decay of the spines in hippocampus, which could be involved in cognitive impairments in schizophrenia.
authors.affiliation: Psychiatry Department, Huashan Hospital of Fudan University, Middle Wu Lu Mu Qi Road, Shanghai 200040, PR China.
authors.forename: Dai
authors.initials: D
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Honglei
authors.initials: H
authors.lastname: Xiao
authors.forename: Georgia C
authors.initials: GC
authors.lastname: Prado Schmidt
authors.forename: Shenxun
authors.initials: S
authors.lastname: Shi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D049229:Dendritic Spines / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016622:Silver Staining; D013550:Swimming; D013997:Time Factors; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: Cdc42; Cognition; MK-801; Rac1; RhoA; Synapse