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Aberrant CaMKII activity in the medial prefrontal cortex is associated with cognitive dysfunction in ADHD model rats.
Yabuki, Yasushi; Shioda, Norifumi; Maeda, Tomomi; Hiraide, Sachiko; Togashi, Hiroko; Fukunaga, Kohji.
Afiliación
  • Yabuki Y; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Shioda N; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Maeda T; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Hiraide S; Department of Pharmacology, Faculty of Pharmaceutical Sciences Health Sciences, University of Hokkaido, Ishikari-Tobetsu, Japan.
  • Togashi H; Department of Pharmacology, Faculty of Pharmaceutical Sciences Health Sciences, University of Hokkaido, Ishikari-Tobetsu, Japan.
  • Fukunaga K; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Electronic address: kfukunaga@m.tohoku.ac.jp.
Brain Res ; 1557: 90-100, 2014 Apr 04.
Article en En | MEDLINE | ID: mdl-24561222
ABSTRACT
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurobehavioral disorder accompanied by cognitive and learning deficits, which is prevalent among boys. Juvenile male stroke-prone spontaneously hypertensive rats (SHRSP) exhibit ADHD-like behaviors including cognitive deficits and represent one animal model of ADHD. Here, we define a mechanism underlying cognitive dysfunction observed in SHRSP. Acute methylphenidate (MPH 1mg/kg, p.o.) administration to SHRSP significantly improved not only inattention in a Y-maze task but also cognitive dysfunction in a novel object recognition test. Interestingly, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity, which is essential for memory and learning acquisition, was excessively elevated in the medial prefrontal cortex (mPFC) but not in the hippocampal CA1 region of SHRSP compared with Wistar-Kyoto (WKY) rats. We also confirmed that elevated CaMKII autophosphorylation in the mPFC causes increased phosphorylation of the CaMKII substrate α-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid-type glutamate receptor subunit 1 (GluR1) (Ser-831). Ca(2+)-dependent phosphorylation levels of factors such as extracellular signal-regulated kinase (ERK) and protein kinase C (PKC) were unchanged in the SHRSP mPFC. Also, protein levels of the dopamine D2 receptor (D2R) but not the dopamine D1 receptor (D1R) were increased in the SHRSP mPFC. Acute MPH (1mg/kg, p.o.) administration attenuated aberrant CaMKII activity and increased GluR1 phosphorylation observed in SHRSP. Taken together, we propose that cognitive impairment in SHRSP is associated with aberrant CaMKII activity in the mPFC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno por Déficit de Atención con Hiperactividad / Corteza Prefrontal / Trastornos del Conocimiento / Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Brain Res Año: 2014 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno por Déficit de Atención con Hiperactividad / Corteza Prefrontal / Trastornos del Conocimiento / Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Brain Res Año: 2014 Tipo del documento: Article País de afiliación: Japón