Attention Deficit Hyperactivity Disorder In Animal Models

§ 1 The behavioural tests of the SHR - an animal model of hyperactivity-impulsivity and/or inattentionObjective To evaluate juvenile spontaneously hypertensive rats (SHR) as an animal model of a developmental disorder, which is diagnosed according to attention deficit/hyperactivity disorder (ADHD). Methods To characterize behavioural alterations, we studied motor activity, as well as attention and cognitive behaviours in juvenile SHR by using open-field environment test, lat maze and step down test. All the behavior in the tests were monitored by a CCD video camera and analyzed off-line. Results (1) Ambulatory and rearing activities in the open-field environment were significantly higher in SHR than in their Wistar-Kyoto (WKY) controls; (2 ) The behavior in a Lat maze during three consecutive 10-min was monitored, frequency of running across the corners and the rearing activities which is used as an index of non-selective attention, were significantly higher in SHR than in WKY during either the 30 minutes or the three consecutive 10-min; (3 ) In step down test, there are no significant difference of acquisition between the SHR and WKY groups. In contrast, on the retention test, there was significant difference between 2 groups. Conclusion Our findings reveal that juvenile SHR manifest behaviours resembling a developmental disorder, attention deficit/hyperactivity disorder (ADHD). § 2 Gene expression profiles in the the prefrontal cortex of SHR using microarray analysisObjective To investigate the difference in gene expression profiles between the prefrontal cortex of SHR and WKY by using microarray analysis, and to analyze the feature of gene expression profiles in the PFC of SHR . Methods The total RNA was extracted from the prefrontal cortex of SHR rats and WKY and gene expression was analyzed using Affymetrix oligonucleotide microarray technology (RAE230A). The functions of the differentially expressed genes were analyzed by bioinformatics. Results (1)209, 60, 23 probe sets genes were found significantly differentially expressed over 2, 4, 8 folds respectively between the prefrontal cortex of SHR and WKY. Removed the probes that was absent in the prefrontal cortex of SHR and WKY, there was 160 probe sets remained. (2) Among the 160 probe sets, there are 66 EST (Expressed Sequence Tag), 21 function-unknown proteins or hypothetical proteins, 67 Unigenes with known function in the differentially expressed genes. (3) Different clusters of genes associated with neuro development, metabolism, signal transduction, DNA transcription, immune, etc were concerned. Conclusion Dysregulation of synaptic transmission, impaired the formation of the mylin of axons, upregulation of DNA transcription-related genes, decreased immunity related genes etc are the features of gene expression profiles of the prefrontal cortex of SHR. § 3 Verification of differentially expressed genes in prefrontal cortex of SHRObjective To verify the expressive levels of the differentially expressed genes in prefrontal cortex of SHR and WKY, and to identify the reliability and confidence level of the result in gene expression profiles of in prefrontal cortex of SHR. Methods The total RNA were extracted from prefrontal cortex of SHR and WKY. Both RT-PCR technique and fluorescent quantitation PCR technique were used to detect the expressive levels of some differentially expressed genes in prefrontal cortex of SHR and WKY . Results (1) By RT-PCR detection, it was found that the expressive levels of Egr1 gene, Dusp1 gene, NGFI-B gene were significantly higher and the expressive levels of RT1-Aw2 gene were significantly lower in prefrontal cortex of SHR than those in WKY. (2) In the studies of fluorescent quantitation PCR, it was found that the expressive level of Arc gene was significantly higher and the expressive levels of Camk4 gene, Sv2b gene were significantly lower in prefrontal cortex of SHR than those in WKY . Conclusion The tendencies in the expressive alteration of all verified differentially expressed genes were in coincidence with the resu...