Annexin a1 and formyl peptide receptor 2/3 like: Interaction between hypothalamic–pituitary–adrenal axis and hippocampal memory in a model of corticosterone‐induced depressive like behavior

Abstract

The activity of the hypothalamic‐pituitary‐adrenal axis is commonly disregulated in stress‐related psychiatric disorders. Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe‐associated molecules. It was demonstrated that Fpr2/3 deficient mice show a distinct profile of behaviour characterised by reduced anxiety. Annexin 1 (ANXA1), an endogenous ligand of Formyl Peptide receptor 2/3 like (FPRL 2/3) is a member of the family of phospholipids and calcium annexes proteins with a well‐defined role in the delayed early inhibitory feedback of glucocorticoids in the pituitary gland. The aim of study was first, to evaluate the potential role of ANXA1 and FPRL 2/3 as mediator cell‐mediator of the inhibitory effects of glucocrticoids on corticotrophin secretion (ACTH), subsequently the possible correlation between depression like behaviour and memory impairment in the hippocampus studying Ras/ERK pathway. C57BL/6 (CORT +), Anx a1 −/− and Fpr 2/3 −/− mice were exposed to corticosterone (35 μ/ml/day) to induce depression like state via drinking water for 28 days and then behavioural test was performed to measure immobility time in the forced swimming test, locomotor activity in the open field test, sucrose consumption in the sucrose preference test, anxiety in the novelty suppressed feeding and short‐term memory, intermediate‐term memory and long‐term memory in the novel object recognition test. Anx a1−/− mice showed an improvement in depression‐like behavior compared to Fpr 2/3 like −/− and CORT + mice. Histological analyses were performed to evaluate the number of neurons in the dentate gyrus, as well as the degree of neurogenesis through the neurotrophic factors of BDNF and GDNF. In conclusion, we can state that the absence of the anx a1 protein, even more than the absence of FPR 2/3, improves the depressive behavior induced by chronic administration of glucocorticoids, as it appears to have a neuroprotective role in the hippocampus following a damage caused from a chronic condition of depressionSupport or Funding Informationno fundingThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.