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首页> 外文期刊>The European Journal of Neuroscience >Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain
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Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain

机译：化学疗法破坏成人大脑的学习，神经发生和θ活性

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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 hypothesised 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'. Chemotherapy disrupts attention, working memory and speed of processing in humans. According to our current results in adult male rats, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis (A and B) and theta activity (C and D) that may explain the selective deficits in processes of learning (E) that describe the 'chemobrain'.
机译：化学疗法，尤其是长时间的化学疗法，会破坏人们的注意力，工作记忆和加工速度。大多数穿过血脑屏障的抗癌药物也会减少成人的神经发生。由于海马中会产生新的神经元，因此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机制通常是未知的。可能的介体是theta范围（3-12 Hz）内的海马振荡活动。 Theta活动可预测和促进健康动物和人类的有效学习。在这里，我们假设化学疗法通过减少海马成年神经发生和theta活性来破坏学习。成年雄性Sprague-Dawley大鼠定期服用替莫唑胺数周。治疗后进行不同类型的眨眼经典调节训练，这是联想学习的一种形式。化学疗法减少了神经发生和内源性theta活性，并破坏了对条件刺激的学习和相关的theta带响应。替莫唑胺的有害作用仅在治疗几周后才发生，并且仅在需要跨时间间隙关联事件的任务上发生，而在训练中没有时间重叠的刺激时才发生。化学疗法并未破坏先前学习的联想的记忆，这种记忆独立于海马（海马中的新神经元）。总之，长时间的全身化疗与海马成年神经发生和theta活性的降低有关，这可能解释了描述“化学障碍”的学习过程中的选择性缺陷。化学疗法破坏了人们的注意力，工作记忆和加工速度。根据我们目前在成年雄性大鼠中的研究结果，长时间的全身化疗与海马成年神经生成（A和B）和theta活性（C和D）的降低有关，这可能解释了学习过程中的选择性缺陷（E） “ chemobrain”。

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