Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment.
Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment.
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DOI：
10.1038/npp.2009.207
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发表时间：
2010-03
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--
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海马区CA3区的过度神经活动与老年大鼠的记忆障碍有关。我们测试了旨在减少这种过度活动的干预措施是否会改善记忆表现。老年(24-28个月)雄性Long-Evans大鼠的空间记忆任务的特征取决于海马体的功能完整性，因此在一系列实验中使用了已发现记忆障碍的老年大鼠。通过腺相关病毒转导在CA3区过表达抑制性神经肽Y 13-36可以改善以损害为特征的老年大鼠的海马依赖长期记忆。随后用两种常用的抗癫痫药物丙戊酸钠和左乙拉西坦进行的实验，在这些老年大鼠中类似地产生了剂量依赖的记忆改善。低剂量的这些药物改善了空间记忆，在开胃和厌恶的空间任务中都被观察到。这些不同治疗方式的好处与这样一个概念是一致的，即海马区CA3区的过度活动是一种功能障碍，可能在海马依赖记忆过程中年龄相关损害的基础上发挥关键作用。由于在功能神经成像中观察到的人类年龄相关性记忆障碍时，海马区激活增加，目前的发现也表明，在认知障碍的老年人中，低剂量的某些抗癫痫药物可能具有治疗潜力，并为这一适应症指明了新的靶点。
Excess neural activity in the CA3 region of the hippocampus has been linked to memory impairment in aged rats. We tested whether interventions aimed at reducing this excess activity would improve memory performance. Aged (24–28 mo-old) male Long-Evans rats were characterized in a spatial memory task known to depend on the functional integrity of the hippocampus, such that aged rats with identified memory impairment were used in a series of experiments. Over-expression of the inhibitory neuropeptide Y 13–36 in the CA3 via adeno-associated viral transduction was found to improve hippocampal-dependent long-term memory in aged rats that had been characterized with impairment. Subsequent experiments with two commonly used antiepileptic agents, sodium valproate and levetiracetam, similarly produced dose-dependent memory improvement in such aged rats. Improved spatial memory with low doses of these agents was observed in both appetitve and aversive spatial tasks. The benefits of these different modalities of treatment are consistent with the concept that excess activity in the CA3 region of the hippocampus is a dysfunctional condition that may play a key role underlying age-related impairment in hippocampal-dependent memory processes. Because increased hippocampal activation occurs in age-related memory impairment in humans as observed in functional neuroimaging, the current findings also suggest that low doses of certain antiepileptic drugs in cognitively impaired elderly humans may have therapeutic potential and point to novel targets for this indication.
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影响因子：
11
作者：
Miller, S. L.;Fenstermacher, E.;Dickerson, B. C.
通讯作者：
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影响因子：
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