Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging
Brain Research Reviews. 2001-11-01; 37(1-3): 301-312
DOI: 10.1016/S0165-0173(01)00135-7
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Vallée M(1), Mayo W, Le Moal M.
Author information:
(1)Institut F. Magendie-INSERM U259, Domaine de Carreire, Rue Camille Saint
Saëns, 33077, Cedex, Bordeaux, France.
Aging is a general process of functional decline which involves in particular a
decline of cognitive abilities. However, the severity of this decline differs
from one subject to another and inter-individual differences have been reported
in humans and animals. These differences are of great interest especially as
concerns investigation of the neurobiological factors involved in cognitive
aging. Intensive pharmacological studies suggest that neurosteroids, which are
steroids synthesized in the brain in an independent manner from peripheral
steroid sources, could be involved in learning and memory processes. This review
summarizes data in animals and humans in favor of a role of neurosteroids in
cognitive aging. Studies in animals demonstrated that the neurosteroids
pregnenolone (PREG) and dehydroepiandrosterone (DHEA), as sulfate derivatives
(PREGS and DHEAS, respectively), display memory-enhancing properties in aged
rodents. Moreover, it was recently shown that memory performance was correlated
with PREGS levels in the hippocampus of 24-month-old rats. Human studies,
however, have reported contradictory results. First, improvement of learning and
memory dysfunction was found after DHEA administration to individuals with low
DHEAS levels, but other studies failed to detect significant cognitive effects
after DHEA administration. Second, cognitive dysfunctions have been associated
with low DHEAS levels, high DHEAS levels, or high DHEA levels; while in other
studies, no relationship was found. As future research perspectives, we propose
the use of new methods of quantification of neurosteroids as a useful tool for
understanding their respective role in improving learning and memory impairments
associated with normal aging and/or with pathological aging, such as Alzheimer’s
disease.