BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder affecting approximately 5% of children and adolescents and 3% of adults, and the prefrontal cortex (PFC) may play the most critical role in the expression of ADHD. Converging previous studies indicate a potential role of Homer--a scaffolding protein family localized at the postsynaptic density (PSD) of glutamatergic excitatory synapses--in behavioral pathologies associated with neuropsychiatric disorders. Accordingly, we speculate that these Homer isoforms might contribute to the etiology and development of ADHD. METHOD: We investigated the differential mRNA and protein expressions of several Homer isoforms in the PFC of the spontaneous hypertensive rat/Wistar-Kyoto rats (SHR/WKY), the most frequently used animal model of ADHD, using RT-PCR and western blotting. Furthermore, we examined the effects of methylphenidate (MPH) exposure on the behaviors and the expression of different Homer isoforms in the PFC of SHR, using Làt maze, RT-PCR and western blotting, respectively. RESULTS: Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at a significantly lower levels in the PFC of SHR compared with WKY. MPH exposure decreased the locomotor activity and non-selective attention of SHR, and it up regulated the expression of Homer 1a and Homer 2a/b, but not Homer 1b/c, in the PFC of SHR. CONCLUSION: It is plausible that Homer 1a and Homer 2a/b may be involved in the etiology and pathogenesis of ADHD. Future work will focus on elucidating the specific mechanisms of Homer 1a and Homer 2a/b in ADHD.
BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder affecting approximately 5% of children and adolescents and 3% of adults, and the prefrontal cortex (PFC) may play the most critical role in the expression of ADHD. Converging previous studies indicate a potential role of Homer--a scaffolding protein family localized at the postsynaptic density (PSD) of glutamatergic excitatory synapses--in behavioral pathologies associated with neuropsychiatric disorders. Accordingly, we speculate that these Homer isoforms might contribute to the etiology and development of ADHD. METHOD: We investigated the differential mRNA and protein expressions of several Homer isoforms in the PFC of the spontaneous hypertensiverat/Wistar-Kyoto rats (SHR/WKY), the most frequently used animal model of ADHD, using RT-PCR and western blotting. Furthermore, we examined the effects of methylphenidate (MPH) exposure on the behaviors and the expression of different Homer isoforms in the PFC of SHR, using Làt maze, RT-PCR and western blotting, respectively. RESULTS: Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at a significantly lower levels in the PFC of SHR compared with WKY. MPH exposure decreased the locomotor activity and non-selective attention of SHR, and it up regulated the expression of Homer 1a and Homer 2a/b, but not Homer 1b/c, in the PFC of SHR. CONCLUSION: It is plausible that Homer 1a and Homer 2a/b may be involved in the etiology and pathogenesis of ADHD. Future work will focus on elucidating the specific mechanisms of Homer 1a and Homer 2a/b in ADHD.
Authors: Klaus V Wagner; Jakob Hartmann; Christiana Labermaier; Alexander S Häusl; Gengjing Zhao; Daniela Harbich; Bianca Schmid; Xiao-Dong Wang; Sara Santarelli; Christine Kohl; Nils C Gassen; Natalie Matosin; Marcel Schieven; Christian Webhofer; Christoph W Turck; Lothar Lindemann; Georg Jaschke; Joseph G Wettstein; Theo Rein; Marianne B Müller; Mathias V Schmidt Journal: Neuropsychopharmacology Date: 2015-03-13 Impact factor: 7.853
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Authors: Qin Hong; Lei Yang; Min Zhang; Xiao-Qin Pan; Mei Guo; Li Fei; Mei-Ling Tong; Rong-Hua Chen; Xi-Rong Guo; Xia Chi Journal: Int J Med Sci Date: 2012-12-27 Impact factor: 3.738
Authors: Douglas Teixeira Leffa; Alana Castro Panzenhagen; Diego Luiz Rovaris; Claiton Henrique Dotto Bau; Luis Augusto Rohde; Eugenio Horacio Grevet; Gabriel Natan Pires Journal: BMJ Open Sci Date: 2018-10-19