Remodeling of neural networks in the anterior forebrain of an animal model of hyperactivity and attention deficits as monitored by molecular imaging probes.
Remodeling of neural networks in the anterior forebrain of an animal model of hyperactivity and attention deficits as monitored by molecular imaging probes. These studies report on the remodeling of neural networks which are likely to be the consequences of the segmental defect in the anterior forebrain of an animal model of hyperactivity and attention-deficit, the juvenile prehypertensive male spontaneously hypertensive rat (SHR). Molecular biology and microscope imaging techniques were used such as: (i) dopamine (DA) D-1 and D-2 receptors by radioligand binding studies; (ii) the Ca2+/Calmodulin-dependent protein kinase II (CaMKII); (iii) transcription factors (TF) such as c-FOS by Immunocytochemistry; and (iv) the respiratory chain enzyme cytochrome-oxidase (C.O.), as markers of neuronal activity in the anterior forebrain of SHR and Wistar Kyoto normotensive (WKY) controls rats. Microcomputer-assisted high-resolution image analysis using DA receptor binding and C.O., as probes revealed by cross-correlations among different regions within brain an altered cross-talk in the anterior forebrain of the SHR as compared to the controls. In particular, an altered cross-talk was also observed within the amygdala complex in the SHR by CaMKII and c-FOS expression. Therefore, the hypothesized segmental defect in the anterior forebrain of the SHR produces network consequences leading to behavioral alteration in the attentional activity and emotional domains. Subchronic treatment with metilphenidate (MP) that is known to block the reuptake of biogenic amines (mainly DA) produced network remodeling which are known to be paralleled by behavioral modifications in the attentive activity and emotional domains. Imperspective, the results from this model system that features the main aspects of attention-deficit hyperactivity disorder (ADHD), can be useful for the understanding of the neural substrates of hyperactivity and attention deficits and possibly for an early diagnosis and appropriate treatment of ADHD children.
Papa
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Institute of Anatomy and Laboratory of Neurophysiological, Behavioral & Neural Networks, F. Bottazzi, II University of Naples, Italy.
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Sadile
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D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology*; D001345:Autoradiography; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D009415:Nerve Net / Q000473:pathology*; D016548:Prosencephalon / Q000473:pathology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011954:Receptors, Dopamine / Q000187:drug effects
D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D011954:Receptors, Dopamine; D008774:Methylphenidate; D003576:Electron Transport Complex IV; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases