2024-03-29T10:54:00Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:02002059
2023-01-16T04:07:05Z
499:500:501
Mice with exonic RELN deletion identified from a patient with schizophrenia have impaired visual discrimination learning and reversal learning in touchscreen operant tasks
Liao, Jingzhu
Dong, Geyao
Wulaer, Bolati
Sawahata, Masahito
Mizoguchi, Hiroyuki
Mori, Daisuke
Ozaki, Norio
Nabeshima, Toshitaka
Nagai, Taku
Yamada, Kiyofumi
open access
© 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
The Reelin gene (RELN) encodes a large extracellular protein, which has multiple roles in brain development and adult brain function. It activates a series of neuronal signal transduction pathways in the adult brain that function in synaptic plasticity, dendritic morphology, and cognitive function. To further investigate the roles of Reln in brain function, we generated a mouse line using the C57BL/6 J strain with the specific Reln deletion identified from a Japanese patient with schizophrenia (Reln-del mice). These mice exhibited abnormal sociality, but the pathophysiological significance of the Reln deletion for higher brain functions, such as learning and behavioral flexibility remains unclear. In this study, cognitive function in Reln-del mice was assessed using touchscreen-based visual discrimination (VD) and reversal learning (RL) tasks. Reln-del mice showed normal learning in the simple VD task, but the learning was delayed in the complex VD task as compared to their wild-type (WT) littermates. In the RL task, sessions were divided into early perseverative phase (sessions with <50% correct) and later learning phase (sessions with ≥50% correct). Reln-del mice showed normal perseveration but impaired relearning ability in both simple RL and complex RL task as compared to WT mice. These results suggest that Reln-del mice have impaired learning ability, but the behavioral flexibility is unaffected. Overall, the observed behavioral abnormalities in Reln-del mice suggest that this mouse model is a useful preclinical tool for investigating the neurobiological mechanism underlying cognitive impairments in schizophrenia and a therapeutic strategy.
Elsevier
2023-01-07
2022-01-07
eng
journal article
AM
http://hdl.handle.net/2237/0002002059
https://nagoya.repo.nii.ac.jp/records/2002059
https://doi.org/10.1016/j.bbr.2021.113569
0166-4328
Behavioural Brain Research
416
113569
https://nagoya.repo.nii.ac.jp/record/2002059/files/manuscript-0728.pdf
application/pdf
2.2 MB
2023-01-07