Insulin-regulated aminopeptidase inhibitor-mediated increases in dendritic spine density are facilitated by glucose uptake
Benjamin Seyer, Shanti Diwakarla, Peta Burns, Anders Hallberg, Alfhild Gronbladh, Mathias Hallberg, Siew Yeen Chai
Journal of Neurochemistry | WILEY | Published : 2019
Ethyl2-acetylamino-7-hydroxy-4-pyridin-3-yl-4H-chromene-3-carboxylate (HFI-419), the benzopyran-based inhibitor of insulin-regulated aminopeptidase (IRAP), has previously been shown to improve spatial working and recognition memory in rodents. However, the mechanism of its cognitive-enhancing effect remains unknown. There is a close correlation between dendritic spine density and learning in vivo and several studies suggest that increases in neuronal glucose uptake and/or alterations to the activity of matrix metalloproteinases (MMPs) may improve memory and increase dendritic spine density. We aimed to identify the potential mechanism by which HFI-419 enhances memory by utilizing rat primary..View full abstract
This work was supported by grants from the Swedish Research Council, the Swedish Brain Foundation, and the Kjell and Marta Beijer Foundation to the Department of Pharmaceutical Biosciences at Uppsala University. Siew Yeen Chai was supported by a National Health and Medical Research Council of Australia, Senior Research Fellowship. The authors also wish to acknowledge that parts of this work have previously appeared in the dissertation of Benjamin John Seyer entitled 'Characterisation of the paradigms used to assess IRAP inhibitors as novel cognitive enhancing agents', Monash University (2017). The authors declare they have no competing interests. All experiments were conducted in compliance with the ARRIVE guidelines.