Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea.
Behav Brain Res. 2022 May 24;426:113836. doi: 10.1016/j.bbr.2022.113836. Epub 2022 Mar 9.
Current antipsychotics have limited effects on the cognitive deficits of schizophrenia patients, therefore, cognitive remediation has been applied to schizophrenia patients to ameliorate cognitive dysfunction. However, the neurobiological mechanisms of cognitive training programs have not been well studied because established animal models are not suitable or because repetitive training has not been introduced in such animal models. In the present study, we employed Toll-like receptor 2 knockout (TLR2 KO) mouse as a schizophrenia mouse model and evaluated the effects of repetitive training as cognitive remediation therapy for schizophrenia. TLR2 KO mice could fully learn the Barnes maze paradigm through repetitive training to improve memory retrieval and reversal learning ability, although the learning speed was slower than that of wild-type (WT) animals. In addition, highly repetitive training activated the neuronal cells in the prefrontal cortex, hippocampal CA3 and hippocampal DG regions of TLR2 KO mice, similar to WT mice. These results indicated that TLR2 KO mouse would be a useful tool for studying the neurobiological mechanisms of cognitive remediation in schizophrenia.
目前的抗精神病药物对精神分裂症患者的认知缺陷的疗效有限，因此，认知矫正已被应用于精神分裂症患者，以改善认知功能障碍。然而，由于没有建立合适的动物模型，或者由于没有在这些动物模型中引入重复训练，认知训练计划的神经生物学机制尚未得到很好的研究。在本研究中，我们采用 Toll 样受体 2 敲除（TLR2 KO）小鼠作为精神分裂症动物模型，并评估了重复训练作为精神分裂症认知矫正治疗的效果。TLR2 KO 小鼠可以通过重复训练充分学习 Barnes 迷宫范式，以提高记忆检索和反转学习能力，尽管学习速度比野生型（WT）动物慢。此外，高度重复训练激活了 TLR2 KO 小鼠前额叶皮质、海马 CA3 和海马 DG 区域的神经元细胞，与 WT 小鼠相似。这些结果表明，TLR2 KO 小鼠将成为研究精神分裂症认知矫正神经生物学机制的有用工具。
