| First Author | Adeosun SO | Year | 2019 |
| Journal | Neurobiol Learn Mem | Volume | 161 |
| Pages | 106-114 | PubMed ID | 30954674 |
| Mgi Jnum | J:290234 | Mgi Id | MGI:6442349 |
| Doi | 10.1016/j.nlm.2019.03.012 | Citation | Adeosun SO, et al. (2019) Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture. Neurobiol Learn Mem 161:106-114 |
| abstractText | We have previously reported cognitive impairments in both young and old mice, particularly in female mice expressing mouse Arg-61 apoE, with a point mutation to mimic the domain interaction feature of human apoE4, as compared to the wildtype mouse (C57BL/6J) apoE. In this study, we further evaluated water maze performance in the female Arg-61 mice at an additional time point and then investigated related hippocampal cyto-architecture in these young female Arg-61 apoE mice vs. the wildtype mice. The results of behavioral performance consistently support our previous report that the young female Arg-61 apoE showed cognitive impairment versus C57BL/6J at the same age. The cyto-architectural results showed that volume of the granular cell layer (GCL) was significantly larger in both 5- and 10-month old Arg-61 apoE mice versus C57BL/6J mice. While the number of newborn calretinin-positive neurons was greater in the sub-granular zone (SGZ) in 5-month old Arg-61 mice, this number dropped significantly in 10-month old Arg-61 mice to a lower level than in age-matched C57BL/6J mice. In addition, the amyloid beta species was significantly higher in 5-month old Arg-61 mice versus age-matched C57BL/6J mice. In conclusion, impaired cognitive functions in female Arg-61 apoE mice appear correlated with larger GCL volume and higher calretinin-positive cell number and suggest a compensatory cellular response that may be related to amyloid beta perturbations early in life. Therefore this study suggests a novel cyto-architectural mechanism of apoE4-dependent pathologies and increased susceptibility of APOEepsilon4 subjects to Alzheimer's disease. |
