| First Author | Androuin A | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 1140 |
| PubMed ID | 30718666 | Mgi Jnum | J:275902 |
| Mgi Id | MGI:6304904 | Doi | 10.1038/s41598-018-37980-y |
| Citation | Androuin A, et al. (2019) Activity-induced MEMRI cannot detect functional brain anomalies in the APPxPS1-Ki mouse model of Alzheimer's disease. Sci Rep 9(1):1140 |
| abstractText | Alzheimer's disease (AD) is the most common cause of dementia. Aside neuropathological lesions, abnormal neuronal activity and brain metabolism are part of the core symptoms of the disease. Activity-induced Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) has been proposed as a powerful approach to visualize evoked brain activity in rodents. Here, we evaluated the relevance of MEMRI in measuring neuronal (dys-)function in the APPxPS1 knocked-in (KI) mouse model of AD. Brain anomalies were firstly demonstrated in APPxPS1-Ki mice using cognitive testing (memory impairment) and histological mapping of immediate early gene products (decreased density of fos-positive neurons). Paradoxically, MEMRI analyses were not able to confirm the occurrence of neuronal hypoactivities in vivo. We then performed a neuropathological analysis that highlighted an abnormal increased permeability of the blood-brain barrier (BBB) in APPxPS1-Ki mice. We hypothesized that diffuse weakening of the BBB results in an uncontrolled diffusion of the MR contrast agent and a lack of correlation between manganese accumulation and neuronal activity. These results bring to light a limitation of the activity-induced MEMRI approach when applied to the APPxPS1-Ki mouse model as well as other mouse models harboring a compromised BBB. |
