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首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >CHRONIC D-AMPHETAMINE ADMINISTERED FROM CHILDHOOD TO ADULTHOOD DOSE-DEPENDENTLY INCREASES THE SURVIVAL OF NEW NEURONS IN THE HIPPOCAMPUS OF MALE C57BL/6J MICE
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CHRONIC D-AMPHETAMINE ADMINISTERED FROM CHILDHOOD TO ADULTHOOD DOSE-DEPENDENTLY INCREASES THE SURVIVAL OF NEW NEURONS IN THE HIPPOCAMPUS OF MALE C57BL/6J MICE

机译：从儿童期到成人期剂量的慢性D-苯丙胺剂量依赖性地增加了男性C57BL / 6J小鼠海马中新神经元的存活

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Adderall is widely prescribed for attention deficit hyperactivity disorder (ADHD) though long term neurological effects of the main ingredient d-amphetamine are not well understood. The purpose of this study was to examine effects of clinically prescribed doses of d-amphetamine and one abuse dose administered from childhood to adulthood on adult hippocampal neurogenesis and activation of the granule layer of the dentate gyrus. Beginning in early adolescence (age 28 days) to adulthood (age 71), male C57BL/6J mice were administered twice daily i.p. injections of vehicle, 0.25, 0.5 or 2 mg/kg d-amphetamine. Locomotor activity was measured in home cages by video tracking. At age 53-56, mice received bromodeoxyuridine (BrdU) injections to label dividing cells. Immunohistochemical detection of BrdU, neuronal nuclear protein (NeuN), double-cortin (DCX) and Ki67 was used to measure neurogenesis and cell proliferation at age 71. AFosB was measured as an indicator of repeated neuronal activation. An additional cohort of mice was treated similarly except euthanized at age 58 to measure activation of granule neurons from d-amphetamine (by detection of c-Fos) and cell proliferation (Ki67) at a time when the fate of BrdU cells would have been determined in the first cohort. d-Amphetamine dose-depen-dently increased survival and differentiation of BrdU cells into neurons and increased number of DCX cells without affecting the number of Ki67 cells. Low doses of d-amphetamine decreased c-Fos and AFosB in the granule layer. Only the high dose induced substantial locomotor stimulation and sensitization. Results suggest both therapeutic and abuse doses of d-amphetamine increase the number of new neurons in the hippocampus when administered from adolescence to adulthood by increasing survival and differentiation of cells into neurons not by increasing progenitor cell proliferation. Mechanisms for amphetamine-induced neurogenesis are unknown but appear activity independent. Results suggest part of the beneficial effects of therapeutic doses of d-amphetamine for ADHD could be via increased hippocampal neurogenesis.
机译：尽管对主要成分d-苯异丙胺的长期神经系统作用尚不十分了解，但Adderall被广泛用于注意力缺陷多动障碍（ADHD）。这项研究的目的是检查从儿童到成年的临床规定剂量的d-苯异丙胺和一种滥用剂量对成年海马神经发生和齿状回颗粒层活化的影响。从青春期早期（28天）到成年（71岁）开始，雄性C57BL / 6J小鼠每天经腹膜内给药两次。注射0.25、0.5或2 mg / kg d-苯丙胺。通过视频跟踪来测量笼中的运动能力。在53-56岁时，小鼠接受了溴脱氧尿苷（BrdU）注射以标记分裂细胞。 BrdU，神经元核蛋白（NeuN），双皮质素（DCX）和Ki67的免疫组织化学检测可用于测量71岁时的神经发生和细胞增殖。AFosB可作为重复神经元激活的指标。除在58岁时安乐死以测量d-苯异丙胺（通过检测c-Fos）对颗粒神经元的激活以及细胞增殖（Ki67）的时间（确定了BrdU细胞的命运）外，对另一组小鼠进行了类似的处理。在第一个队列中。 d-苯丙胺剂量依赖性地增加BrdU细胞向神经元的存活和分化，并增加DCX细胞的数量，而不影响Ki67细胞的数量。低剂量的d-苯异丙胺可降低颗粒层中的c-Fos和AFosB。只有高剂量诱导大量的运动刺激和致敏作用。结果表明，当从青春期到成年期服用时，治疗剂量和滥用剂量的d-苯丙胺都会增加海马的新神经元数量，而不是通过增加祖细胞增殖来增加细胞的存活和分化为神经元。苯丙胺诱导神经发生的机制尚不清楚，但似乎与活性无关。结果表明，治疗剂量的d-苯异丙胺对ADHD的部分有益作用可能是通过增加海马神经发生。

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