Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain.
Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain.
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化学疗法破坏了成人大脑中的学习，神经发生和THETA活性。
DOI：
10.1111/ejn.12007
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Shors TJ
中科院分区：
文献类型：
--
作者：
Nokia MS;Anderson ML;Shors TJ
化疗，尤其是长期化疗，会扰乱人类的注意力、工作记忆和处理速度。大多数穿过血脑屏障的抗癌药物也会减少成人神经发生。由于新的神经元是在海马体中产生的，这种减少可能会导致工作记忆和相关思维过程的缺陷。这些缺陷背后的神经生理学机制通常是未知的。一个可能的调节因素是海马在 theta 范围（3-12 Hz）内的振荡活动。 Theta 活动可预测并促进健康动物和人类的高效学习。在这里，我们假设化疗通过减少海马成人神经发生和 theta 活动来扰乱学习。将替莫唑胺以循环方式给予成年雄性斯普拉格-道利大鼠几周。治疗后进行不同类型的眨眼经典条件反射训练，这是一种联想学习的形式。化疗减少了神经发生和内源性 θ 活性，并扰乱了学习和对条件刺激的相关 θ 带反应。替莫唑胺的有害影响仅在治疗几周后发生，并且仅发生在需要跨时间间隙关联事件的任务上，而不是在具有时间重叠刺激的训练期间发生。化疗不会破坏先前习得的关联的记忆，这种记忆独立于海马体（新神经元）。总之，长期全身化疗与海马成人神经发生和 theta 活动的减少有关，这可能解释了描述“化学脑”的学习过程中的选择性缺陷。
Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood–brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3–12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesized that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague–Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta-band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the ‘chemobrain’.
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