Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to map the neural substrates of attention-deficit hyperactivity disorder (ADHD) in the spontaneously hypertensive rat (SHR), which is thought to be a model for ADHD. To this aim, the Ca2+/calmodulin-dependent protein kinase II (CaMKII) and transcription factors (TF) were used as markers. The focus of interest was the nucleus accumbens complex (ACB) which is thought to be an interface between limbic and motor systems. Juvenile, male rats of the SHR line and Wistar-Kyoto (WKY) controls were perfused and the brains processed for immunocytochemistry for CaMKII and the TF peptides of the FOS, JUN-B and ZIF-268 families. The results revealed that: (i) in both groups there were more CaMKII-positive neurones in the shell than in the core of the ACB; (ii) SHR had a reduced number of CaMKII-positive elements in anterior portions of the shell; and (iii) SHR had a lower expression of peptide products of the FOS family (c-FOS, in particular) and ZIF-268. In addition, there was a lower expression of c-FOS and zif-268 in the core of the ACB in the SHR. In contrast, there was an increased basal level of JUN-B in the core of the ACB of SHR. The reduced number of CaMKII and TF-positive elements in the most rostral portions of the accumbal complex of SHR, associated to the higher number of binding sites for the DA D-1/D-5 subtype, appears as a discrete alteration in the prosomeric development of the anterior basal forebrain and could be the key to the understanding of ADHD.
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PMID:Reduced transduction mechanisms in the anterior accumbal interface of an animal model of Attention-Deficit Hyperactivity Disorder. 970 49

Molecular biology and microscope imaging techniques were used to map putative neural substrates of hyperactivity and attention deficit in an animal model, the juvenile prehypertensive male spontaneously hypertensive rat (SHR). We have studied in anterior forebrain sections of SHR and Wistar-Kyoto Normotensive (WKY) controls the spatial distribution of neural markers such as: (i) dopamine (DA) D-1 and D-2 receptor families by radioligand binding studies; (ii) the Ca2+/calmodulin-dependent protein kinase II (CaMKII); and (iii) the transcription regulators of gene expression (TFs) c-FOS and JUN-B by Immunocytochemistry (ICC). Microcomputer-assisted high-resolution image analysis showed in the SHR a higher density of DA D-1 receptors and a lower density of D-3 autoreceptors paralleled by a reduced number of elements positive for CaMKII and TFs in a restricted segment of the anterior forebrain that included the most rostral portions of the caudate-putamen, pole and shell of the nucleus accumbens and olfactory tubercle. The differential rostro-caudal distribution of D-1 receptors and D-3 autoreceptors is discussed in the light of current hypotheses of DA mesocorticolimbic system functioning. In addition, the segmental defect was partially reversed by subchronic treatment with a DA re-uptake blocker, Methylphenidate (MPH; 3 mg/kg) and by environmental stimulation during the fifth and sixth postnatal week. The findings are consistent with the role of genetic determinants and environmental factors in the phenotypic expression of hyperactivity and attention deficit.
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PMID:Multiple evidence of a segmental defect in the anterior forebrain of an animal model of hyperactivity and attention deficit. 1065 74