Activity-induced MEMRI cannot detect functional brain anomalies in the APPxPS1-Ki mouse model of Alzheimer’s disease

Abstract : 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.
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Alexandre Androuin, Yah-Se Abada, Myriam Ly, Mathieu Santin, Alexandra Petiet, et al.. Activity-induced MEMRI cannot detect functional brain anomalies in the APPxPS1-Ki mouse model of Alzheimer’s disease. Scientific Reports, Nature Publishing Group, 2019, 9, pp.1140. ⟨10.1038/s41598-018-37980-y⟩. ⟨hal-02017552⟩

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