title: Homer expression in the hippocampus of an animal model of attention-deficit/hyperactivity disorder.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder. We previously demonstrated differential expression of some isoforms of Homer, a family of scaffolding proteins localized to the postsynaptic density of glutamatergic excitatory synapses, in the spontaneous hypertensive rat (SHR), which is the most frequently used animal model of ADHD. Since these changes were observed in the prefrontal cortex (PFC), a critical structure in ADHD, it was hypothesized that these Homer isoforms may play a role in ADHD. The present study aimed to extend these findings to the hippocampus, which has direct connections to the PFC and subserves attention and cognition, two functions that are disturbed in ADHD. Hippocampal mRNA and protein expression of several Homer isoforms were investigated in both SHR and control Wistar-Kyoto (WKY) rats using reverse transcription-polymerase chain reaction and Western blotting, respectively. Both mRNA and protein for Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at significantly lower levels in the hippocampus of SHR compared to WKY rats. The effects of methylphenidate (MPH) on spatial learning and memory in SHRs were also examined using the Morris water maze and on hippocampal expression of Homer isoforms. MPH improved spatial learning and memory and up-regulated hippocampal expression of Homer 1a and Homer 2a/b, but not Homer 1b/c, in SHRs. The animal model of ADHD may have altered expression of Homer 1a and Homer 2a/b in the hippocampus, in addition to the PFC. Future studies will focus on elucidating the specific mechanisms of Homer 1a and Homer 2a/b in ADHD.
authors.affiliation: Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing 210004, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hong
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Pan
authors.forename: Mei
authors.initials: M
authors.lastname: Guo
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Tong
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Chen
authors.forename: Xi-Rong
authors.initials: XR
authors.lastname: Guo
authors.forename: Xia
authors.initials: X
authors.lastname: Chi
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D006624:Hippocampus / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008774:Methylphenidate / Q000627:therapeutic use; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D002352:Carrier Proteins; D018765:Dopamine Uptake Inhibitors; D000072233:Homer Scaffolding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D008774:Methylphenidate