Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical, and morphological investigations.
Hormones and Behavior. 2001-09-01; 40(2): 215-217
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1. Horm Behav. 2001 Sep;40(2):215-7.
Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical,
and morphological investigations.
Mayo W(1), Le Moal M, Abrous DN.
(1)INSERM U259, Institut François Magendie, Rue Camille Saint-Saens, 33077
Bordeaux Cedex, France.
Neurosteroids are a subclass of steroids that can be synthesized in the central
nervous system independently of peripheral sources. Several neurosteroids
influence cognitive functions. Indeed, in senescent animals we have previously
demonstrated a significant correlation between the cerebral concentration of
pregnenolone sulfate (PREG-S) and cognitive performance. Indeed, rats with memory
impairments exhibited low PREG-S concentrations compared to animals with correct
memory performance. Furthermore, these memory deficits can be reversed by
intracerebral infusions of PREG-S. Neurotransmitter systems modulated by this
neurosteroid were unknown until our recent report of an enhancement of
acetylcholine (ACh) release in basolateral amygdala, cortex, and hippocampus
induced by central administrations of PREG-S. Central ACh neurotransmission is
involved in the regulation of memory processes and is affected in normal aging
and in human neurodegenerative pathologies like Alzheimer’s disease. ACh
neurotransmission is also involved in the modulation of sleep-wakefulness cycle
and relationships between paradoxical sleep and memory are well documented in the
literature. PREG-S infused at the level of ACh cell bodies induces a dramatic
increase of paradoxical sleep in young animals. Cognitive dysfunctions,
particularly those observed in Alzheimer’s disease, have also been related to
alterations of cerebral plasticity. Among these mechanisms, neurogenesis has been
recently studied. Preliminary data suggest that PREG-S central infusions
dramatically increase neurogenesis. Taken together these data suggest that PREG-S
can influence cognitive processes, particularly in senescent subjects, through a
modulation of ACh neurotransmission associated with paradoxical sleep
modifications; furthermore our recent data suggest a role for neurosteroids in
the modulation of hippocampal neurogenesis.
Copyright 2001 Academic Press.
PMID: 11534985 [Indexed for MEDLINE]