Young Jared W, Crawford Nicola, Kelly John S, Kerr Lorraine E, Marston Hugh M, Spratt Christopher, Finlayson Keith, Sharkey John
Astellas CNS Research in Edinburgh, The University of Edinburgh, The Chancellor's Building, 49 Little France Crescent, EH16 4SB, UK.
Eur Neuropsychopharmacol. 2007 Jan 15;17(2):145-55. doi: 10.1016/j.euroneuro.2006.03.008. Epub 2006 May 2.
alpha7-Nicotinic acetylcholine receptors (alpha7-nAChR) have been implicated in a range of cognitive deficits in schizophrenia. Therefore we examined alpha7-nAChR knockout (KO), heterozygote (HT) and wildtype (WT) littermate mice in the 5-CSR (a rodent model of sustained attention) and odour span (a novel mouse working memory paradigm) tasks, and related performance to nAChR density. Whilst there was no difference between groups in baseline 5-CSR task performance, alpha7-nAChR KO's exhibited significantly higher omission levels compared to WT mice on increasing the attentional load, with HT mice performing at an intermediate level. Furthermore, alpha7-nAChR KO mice were significantly impaired in the odour span task when compared to WT mice, in a pattern consistent with impaired attention. These behavioural deficits were associated with the loss of alpha7-nAChRs, as alpha4beta2-nAChR density was unaltered in these mice. Thus these studies intimate that the attentional impairment in alpha7-nAChR transgenic mice maybe core to other deficits in cognition.
α7-烟碱型乙酰胆碱受体（α7-nAChR）与精神分裂症的一系列认知缺陷有关。因此，我们在5-CSR（一种持续注意力的啮齿动物模型）和气味跨度（一种新的小鼠工作记忆范式）任务中检查了α7-nAChR基因敲除（KO）、杂合子（HT）和野生型（WT）同窝小鼠，并将其表现与nAChR密度相关联。虽然在基线5-CSR任务表现上各组之间没有差异，但在增加注意力负荷时，α7-nAChR基因敲除小鼠与野生型小鼠相比表现出明显更高的遗漏水平，杂合子小鼠表现处于中间水平。此外，与野生型小鼠相比，α7-nAChR基因敲除小鼠在气味跨度任务中明显受损，其模式与注意力受损一致。这些行为缺陷与α7-nAChR的缺失有关，因为这些小鼠中α4β2-nAChR密度未改变。因此，这些研究表明α7-nAChR转基因小鼠的注意力损害可能是其他认知缺陷的核心。
