Papa M, Sellitti S, Sadile A G
Institute of Anatomy and Laboratory of Neurophysiological, Behavioral & Neural Networks, F. Bottazzi, II University of Naples, Italy.
Neurosci Biobehav Rev. 2000 Jan;24(1):149-56. doi: 10.1016/s0149-7634(99)00052-4.
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.
通过分子成像探针监测多动和注意力缺陷动物模型前脑神经网络的重塑。这些研究报告了神经网络的重塑情况，这可能是多动和注意力缺陷动物模型（幼年高血压前期雄性自发性高血压大鼠，SHR）前脑节段性缺陷的结果。使用了分子生物学和显微镜成像技术，如：（i）通过放射性配体结合研究检测多巴胺（DA）D-1和D-2受体；（ii）检测钙/钙调蛋白依赖性蛋白激酶II（CaMKII）；（iii）通过免疫细胞化学检测转录因子（TF），如c-FOS；（iv）检测呼吸链酶细胞色素氧化酶（C.O.），作为SHR和Wistar Kyoto正常血压（WKY）对照大鼠前脑神经元活动的标志物。使用DA受体结合和C.O.作为探针的微计算机辅助高分辨率图像分析显示，与对照组相比，SHR前脑不同区域之间的交叉相关性发生改变，表明其前脑存在串扰改变。特别是，通过CaMKII和c-FOS表达，在SHR的杏仁核复合体中也观察到串扰改变。因此，假设的SHR前脑节段性缺陷产生了网络后果，导致注意力活动和情绪领域的行为改变。已知能阻断生物胺（主要是DA）再摄取的哌甲酯（MP）进行亚慢性治疗产生了网络重塑，这与注意力活动和情绪领域的行为改变平行。从这个具有注意力缺陷多动障碍（ADHD）主要特征的模型系统得出的结果，可能有助于理解多动和注意力缺陷的神经基础，并可能有助于ADHD儿童的早期诊断和适当治疗。
