Hormetic influence of glucocorticoids on human memory

Abstract

In this paper, we discuss the effects of glucocorticoids on human learning and memory using the recent model of hormesis proposed by Calabrese and collaborators. Although acute increases in glucocorticoids have been shown to impair memory function in humans, other studies report no such impairments or, in contrast, beneficial effects of acute glucocorticoid increases on human memory function. We summarize these studies and assess whether the wealth of data obtained in humans with regard to the effects of acute increase of glucocorticoids on human cognition are in line with a hormetic function. We then discuss several factors that will have to be taken into account in order to confirm the presence of a hormetic function between glucocorticoids and human cognitive performance.

Keywords: Frontal; Glucocorticoids; Hippocampus; Hormesis; Humans; Memory; Noradrenergic Hormones; Receptors.

FIGURE 1

Schematic representation of a hormetic function (Figure adapted from Calabrese and Baldwin, 2003).

FIGURE 2

Schematic representation of the hormetic function relating circulating levels of glucocorticoids and memory performance. The different ratio of occupancy of MRs and GRs at different circulating levels of glucocorticoids are depicted. The lines within each box represent the relative level of occupancy of each receptor type.

FIGURE 3

Schematic representation of the theoretical change in the shape of the inverted-U shape function glucocorticoids, and memory performance with down-regulation of GRs. Group #1 represents individuals with normal levels of GRs, while Group #2 represents individuals with a down-regulation of GRs.