title: Increased locomotor activity and non-selective attention and impaired learning ability in SD rats after lentiviral vector-mediated RNA interference of Homer 1a in the brain.
abstract: Our previous studies found that Homer 1a, a scaffolding protein localized at the post-synaptic density (PSD) of glutamatergic excitatory synapses, is significantly down-regulated in the brain of spontaneous hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). Furthermore, a first-line treatment drug for ADHD, methylphenidate, can up-regulate the expression of Homer 1a. To investigate the possible role of Homer 1a in the etiology and pathogenesis of ADHD, a lentiviral vector containing miRNA specific for Homer 1a was constructed in this study. Intracerebroventricular injection of this vector into the brain of Sprague Dawley (SD) rats significantly decreased Homer 1a mRNA and protein expression levels. Compared to their negative controls, these rats displayed a range of abnormal behaviors, including increased locomotor activity and non-selective attention and impaired learning ability. Our results indicated that Homer 1a down-regulation results in deficits in control over behavioral output and learning similar to ADHD.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hong
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
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: Li
authors.initials: L
authors.lastname: Fei
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 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors; D000072233:Homer Scaffolding Proteins; D006801:Humans; D007276:Injections, Intraventricular; D016086:Lentivirus; D008774:Methylphenidate / Q000008:administration & dosage; D009043:Motor Activity / Q000235:genetics*; D034622:RNA Interference; D051381:Rats
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D008774:Methylphenidate
keywords: ADHD; Homer 1a; RNAi; behavior.; lentiviral vector