Desmarais, Frederik; Hervé, Vincent; Bergeron, Karl-F.; Ravaut, Gaetan; Perrotte, Morgane; Fyfe-Desmarais, Guillaume; Rassart, Eric; Ramassamy, Charles et Mounier, Catherine
(2021).
« Cerebral Apolipoprotein D exits the brain and accumulates in peripheral tissues ». Prépublication.
(Montréal, Québec, Canada, UQAM, INRS, CERMO-FC).
20 p.
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Résumé
Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid me-tabolism. In rodent, the bulk of its expression occurs in the central nervous system. Despite this, ApoD has profound effects in peripheral tissues, indicating that neural ApoD may reach pe-ripheral organs. We endeavour to determine if cerebral ApoD can reach the circulation and ac-cumulate in peripheral tissues. 3 hours was necessary for over 40% of all the radiolabeled human ApoD (hApoD), injected bilaterally, to exit the CNS. Once in circulation, hApoD accumulates mostly in the kindeys/urine, liver, and muscles. Accumulation specificity of hApoD in these tis-sues was strongly correlated with the expression of lowly glycosylated basigin (BSG, CD147). hApoD was observed to pass through bEnd.3 blood brain barrier endothelial cells monolayers. However, cyclophilin A did not impact hApoD internalisation rates in bEnd.3, indicating that ApoD exit from the brain is either independent of BSG or relies on additional cell types. Overall, our data shows that ApoD can quickly and efficiently exit the CNS and reach the liver and kid-neys/urine, organs linked to the recycling and excretion of lipids and toxins. This indicates that cerebral overexpression during neurodegenerative episodes may serve to evacuate neurotoxic ApoD ligands from the CNS.
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