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首页> 外文期刊>The European Journal of Neuroscience >Differential regulation of psychostimulant-induced gene expression of brain derived neurotrophic factor and the immediate-early gene Arc in the juvenile and adult brain.
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Differential regulation of psychostimulant-induced gene expression of brain derived neurotrophic factor and the immediate-early gene Arc in the juvenile and adult brain.

机译：幼年和成年大脑中心理刺激剂诱导的脑源性神经营养因子基因表达和早期基因Arc的差异调节。

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Psychostimulant drugs are widely used in children for the treatment of attention-deficit/hyperactivity disorder. Recent animal studies have suggested that exposure to these agents in early life could be detrimental to brain development. Here, for the first time, the effect of methylphenidate (MPH) and D-amphetamine (AMPH) on the expression of two key genes for neuronal development and plasticity, brain-derived neurotrophic factor (bdnf) and the effector immediate early gene activity-regulated, cytoskeletal-associated protein (Arc), was examined in both juvenile and adult rats. Both MPH [2 mg/kg, intraperitoneal (i.p.)] and AMPH (0.5 mg/kg, i.p.) induced marked decreases of bdnf mRNA in hippocampal and cortical brain regions of juveniles, whereas effects in adults were significantly less (hippocampus) or opposite (frontal cortex). In comparison, Arc mRNA was decreased (hippocampus and parietal cortex), largely unaffected (frontal cortex) or increased (striatum) in juveniles, whereas in adults, Arc mRNA increased in most brain regions. MPH-induced locomotion was also measured, and showed a much smaller increase in juveniles than in adults. In summary, our data show that the effects of MPH and AMPH on expression of the neurodevelopmentally important genes, bdnf and Arc, differ markedly in juvenile and adult rats, with juveniles showing evidence of brain region-specific decreases in both genes. These age-dependent effects on gene expression may be linked with the reported long-term harmful effects of psychostimulants in animal models.
机译：精神兴奋药广泛用于儿童中，用于治疗注意力缺陷/多动症。最近的动物研究表明，在生命早期接触这些药物可能对大脑发育有害。在这里，哌醋甲酯（MPH）和D-苯异丙胺（AMPH）首次对两个神经元发育和可塑性关键基因，脑源性神经营养因子（bdnf）和效应子即刻早期基因活性的表达产生了影响-在幼年和成年大鼠中都检查了调节的细胞骨架相关蛋白（Arc）。 MPH [2 mg / kg，腹膜内（ip）]和AMPH（0.5 mg / kg，ip）均可引起青少年海马和皮质脑区bdnf mRNA的显着降低，而对成年人的影响显着降低（海马）或相反（额叶皮层）。相比之下，在青少年中，Arc mRNA减少（海马和顶叶皮层），大部分未受影响（额叶皮层）或增加（纹状体），而在成年人中，Arc mRNA在大多数大脑区域增加。还测量了MPH引起的运动，并显示与成年人相比，青少年的增长幅度要小得多。总而言之，我们的数据表明，在幼年和成年大鼠中，MPH和AMPH对神经发育重要基因bdnf和Arc的表达的影响明显不同，其中幼年表明这两个基因的大脑区域特异性降低。这些对基因表达的年龄依赖性影响可能与精神兴奋剂在动物模型中的长期有害影响有关。

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