Endocrine Abstracts

Brain ageing associates decreased neuronal plasticity, increased glucocorticoid and decreased retinoic acid (RA) signalling. We previously showed an interaction of these pathways on the regulation of a synaptic plasticity gene, BDNF. We thus investigated the effects of GC and RA on two BDNF-dependent genes: activity-regulated cytoskeleton protein (Arc) and Ca²⁺/calmodulin-dependent protein kinase II (CaMK). Dexamethasone (Dex, 10⁻⁶ M) and/or RA (10⁻⁶ M) were applied on HT22 hippocampal cells during 4 days. Dex significantly decreased (55%) whereas RA increased cellular (145%) CaMKII mRNA compared to control. When combined RA reduced Dex effect. Dex alone did not affect (95%) whereas RA increased (195%) Arc mRNA levels. When combined to Dex RA had the same effect on Arc mRNA as when used alone. As plasticity is closely related to the formation of cell processes, we investigated cell morphology and F-actin cytoskeleton organisation. Dex affected cell morphology: Dex-treated cells areas were significantly larger and rounder than controls and these increases were suppressed when RA was added. Actin expression (mRNA) and abundance (protein) were unchanged by Dex or RA.

Conversely, phalloidin-stained polymerised actin was doubled by Dex. RA suppressed this effect. Both cortical actin and stress fibres were significantly increased by Dex (276% of control). RA suppressed this effect down to the level attained with RA alone: either moderately increased (190%) for cortical actin or decreased under control level for stress fibres (79%). Both glucocorticoids and RA target cell actin cytoskeleton and subsequently cell remodelling. The positive effects of RA on memory processes may then be due to counteracting some of the deleterious effects of glucocorticoids observed in brain ageing.

Disclosure: This study was supported by the Conseil Régional d’Aquitaine and the University of Bordeaux1.