Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome
Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome
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DOI：
10.1038/nn1860
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发表时间：
2007-04-01
影响因子：
25
通讯作者：
Garner, Craig C.
中科院分区：
文献类型：
--
作者：
Fernandez, Fabian;Morishita, Wade;Garner, Craig C.
Ts65Dn 小鼠是唐氏综合症的模型，其齿状回受到过度抑制，这种情况可能会损害突触可塑性和记忆处理。我们发现，用非癫痫剂量的 GABA(A) 拮抗剂对这些小鼠进行长期全身治疗会导致药物后认知持续恢复和长期增强。这些结果表明，过度抑制会导致与唐氏综合症相关的智力障碍，并且 GABA(A) 拮抗剂可能是治疗这种疾病的有用药物。
Ts65Dn mice, a model for Down syndrome, have excessive inhibition in the dentate gyrus, a condition that could compromise synaptic plasticity and mnemonic processing. We show that chronic systemic treatment of these mice with GABA(A) antagonists at non-epileptic doses causes a persistent post-drug recovery of cognition and long-term potentiation. These results suggest that over-inhibition contributes to intellectual disabilities associated with Down syndrome and that GABA(A) antagonists may be useful therapeutic agents for this disorder.