Fernandez Fabian, Morishita Wade, Zuniga Elizabeth, Nguyen James, Blank Martina, Malenka Robert C, Garner Craig C
Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California 94304-5485, USA.
Nat Neurosci. 2007 Apr;10(4):411-3. doi: 10.1038/nn1860. Epub 2007 Feb 25.
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 GABAA 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 GABAA antagonists may be useful therapeutic agents for this disorder.
Ts65Dn小鼠是唐氏综合征的一种模型，其齿状回存在过度抑制，这种情况可能会损害突触可塑性和记忆处理。我们发现，以非癫痫剂量对这些小鼠进行GABAA拮抗剂的慢性全身治疗会导致药物后认知和长期增强的持续恢复。这些结果表明，过度抑制导致了与唐氏综合征相关的智力障碍，并且GABAA拮抗剂可能是治疗这种疾病的有效药物。
