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Neurosteroids and cholinergic systems: implications for sleep and cognitive processes and potential role of age-related changes

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Abstract

Rationale

The neurosteroids pregnenolone sulfate (PREGS), dehydroepiandrosterone sulfate (DHEAS) and allopregnanolone (3α,5α 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 3α,5α 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.

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Acknowledgments

Supported by INSERM, Université de Bordeaux II, and the European Community (QLK6-CT-2000-00179).

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  1. INSERM, U588, Institut François Magendie, Université de Bordeaux II, F-33077, Bordeaux, France

    Olivier George, Monique Vallée, Michel Le Moal & Willy Mayo

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  1. Olivier George
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  2. Monique Vallée
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  3. Michel Le Moal
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  4. Willy Mayo
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Correspondence to Olivier George.

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George, O., Vallée, M., Le Moal, M. et al. Neurosteroids and cholinergic systems: implications for sleep and cognitive processes and potential role of age-related changes. Psychopharmacology 186, 402–413 (2006). https://doi.org/10.1007/s00213-005-0254-6

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