Endocrine Abstracts

Introduction: Hippocampus is a key area in the brain and influences the neuroendocrine functions, especially the hypothalamo–pituitary–adrenal (HPA) axis that is mainly regulated by corticotrophin-releasing hormone (CRH), vasopressin (ADH) and glucocorticoid (GC). This feed-back action is mediated by both glucocorticoid (GRs) and mineralocorticoid (MRs) receptors. GRs are distributed throughout the brain, but mostly in hypothalamic neurons, while the MRs highest expression has been detected in the hippocampus. Aim of the study was to clarify the role of fludrocortisone (MRs agonist) and spironolactone (MRs antagonist) on cell proliferation, differentiation and survival in adult rat hippocampal progenitor (AHP) cells, a totipotent cell line that can differentiate in neurons and glial cells. Furthermore we investigated the effect of fludrocortisone on AHP cell survival after treatment with amyloid β-protein (fragment 1–42).

Methods: AHP cells were cultured with neural stemline medium enriched with FGF-basic. The presence of GRs and MRs was evaluated by RT-PCR. Cell survival was measured by MTT assay and cell proliferation by BrdU incorporation. Apoptosis was studied by Caspase-3 activity analysis. Activation of survival signalling pathways was determined by Western blotting, i.e. phosphorylation of phosphatidylinositol 3-kinase/Akt (PI3K/Akt), glycogen synthase kinease-3 (GSK-3β) and of cAMP response element binding (CREB).

Results: Fludrocortisone, but not spironolactone, stimulates proliferation, and protects against growth factor deprivation-induced apoptosis. Fludrocortisone activates the GSK-3β, the PI3K/Akt and the CREB pathways. Moreover it counteracts the effect of the amyloid β-protein (1–42) on cell death and inhibition of cell proliferation.

Conclusion: The survival and proliferative effect of fludrocortisone in neuronal precursors candidate MRs agonists as potential molecules in the treatment of neurodegenerative conditions, such as Alzheimer′s disease.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.