Neurosteroids and cholinergic systems: Implications for sleep and cognitive processes and potential role of age-related changes
Psychopharmacology. 2006-01-17; 186(3): 402-413
DOI: 10.1007/s00213-005-0254-6
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George O(1), Vallée M, Le Moal M, Mayo W.
Author information:
(1)INSERM, U588, Institut François Magendie, Université de Bordeaux II, F-33077,
Bordeaux, France.
RATIONALE: The neurosteroids pregnenolone sulfate (PREGS),
dehydroepiandrosterone sulfate (DHEAS) and allopregnanolone (3alpha,5alpha
THPROG) have been implicated as powerful modulators of memory processes and
sleep states in young and aged subjects with memory impairment. As these
processes depend on the integrity of cholinergic systems, a specific effect of
neurosteroids on these systems may account for their effects on sleep and
memory.
OBJECTIVE: To review the evidence for a specific and differential effect of
neurosteroids on cholinergic systems.
METHODS: We carried out keyword searches in “Medline” to identify articles
concerning (1) the effects of neurosteroids on cholinergic systems, sleep and
memory processes, and (2) changes in neurosteroid concentrations during aging.
Few results are available for humans. Most data concerned rodents.
RESULTS: Peripheral and central administrations of PREGS, DHEAS, and
3alpha,5alpha THPROG modulate the basal forebrain and brainstem projection
cholinergic neurons but not striatal cholinergic interneurons. Local
administration of neurosteroids to the basal forebrain and brainstem cholinergic
neurons alters sleep and memory in rodents. There are a few conflicting reports
concerning the effects of aging on neurosteroid concentrations in normal and
pathological conditions.
CONCLUSIONS: The specific modulation of basal forebrain and brainstem
cholinergic systems by neurosteroids may account for the effects of these
compounds on sleep and memory processes. To improve our understanding of the
role of neurosteroids in cholinergic systems during normal and pathological
aging, we need to determine whether there is specific regionalization of
neurosteroids, and we need to investigate the relationship between neurosteroid
concentrations in cholinergic nuclei and age-related sleep and memory
impairments.
DOI: 10.1007/s00213-005-0254-6
PMID: 16416333 [Indexed for MEDLINE]