Investigating the Unexpected Effect of Bulkheads in a Dementia Model of Mice Through Molecular Analysis of the Hippocampus

Aim: This study aimed to evaluate the impact of long-term exposure to physical barriers used as preventive measures during the coronavirus disease 2019 (COVID-19) pandemic on cognitive function and behavior in an apolipoprotein E^-/- (ApoE^-/-) mouse dementia model.

Methods: ApoE^-/- mice were divided into co-housed, partitioned by a transparent bulkhead (partitioned), and isolated groups. To assess anxiety, cognitive recognition, and spatial learning, behavioral tests, including the open-field test, novel object recognition test, and Morris water maze test, were conducted at three and six months after the start of the 33-week rearing period. RNA-sequencing analysis of hippocampal tissues was performed to investigate gene expression changes.

Results: The partitioned group exhibited reduced exploratory behavior, lower recognition index, and impaired spatial learning compared with the co-housed group. However, the differences were not significant. Based on morphological analysis, the partitioned and isolated groups presented a significant reduction in neuronal density in the hippocampal CA1 region. RNA-sequencing analysis showed significant changes in the expression of genes related to neurotransmitter transport, neurite outgrowth, and neuropeptide signaling pathways.

Conclusions: Prolonged physical isolation, even with visual contact, can adversely affect cognitive function and hippocampal structure in dementia models. Changes in gene expression indicate that neurotransmitter imbalances and neuroinflammatory responses may contribute to these effects. These findings emphasize the need to develop new infection-prevention measures for patients with dementia during the COVID-19 pandemic.