Pregnenolone sulfate increases hippocampal acetylcholine release and spatial recognition

Darnaudéry, Muriel; Koehl, Muriel; Piazza, Pier-Vincenzo; Moal, Michel Le; Mayo, Willy

doi:10.1016/s0006-8993(99)01964-2

Cited by 68 publications

(35 citation statements)

References 37 publications

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“…Whereas the preventive effect of ICV-injected PREGS on experimental amnesia has been reported in several studies (25), only one report, to the best of our knowledge, has mentioned a promnestic effect of the neurosteroid after ICV administration in rats tested in a spatial recognition task (5). In the present study, results are supportive of a direct improvement by ICV injection of PREGS on memory retention.…”

Section: Discussionsupporting

confidence: 78%

“…Among them, the neurosteroid pregnenolone sulfate (3␤-hydroxy-5-pregnen-20-one sulfate, PREGS) has been well described as a potent steroidal enhancer of learning and memory processes in rodents (1)(2)(3)(4)(5)(6). Of particular interest is the physiological role of PREGS in the hippocampus, which was recently demonstrated for the preservation of age-related spatial memory loss (4).…”

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confidence: 99%

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The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?

Akwa

Ladurelle

Covey

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

127

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The demonstration that the neurosteroid pregnenolone sulfate (PREGS) is active on memory function at both the physiological and pharmacological levels led to us examining in detail the effects of the steroid on spatial working memory by using a two-trial recognition task in a Y-maze, a paradigm based on the natural drive in rodents to explore a novel environment. Dose-response studies in young male adult Sprague-Dawley rats and Swiss mice, after the postacquisition intracerebroventricular injection of steroid, showed an U-inverted curve for memory performance and indicated a greater responsiveness in rats compared with mice. Remarkably, the synthetic (؊) enantiomer of PREGS not only also displayed promnesiant activity, but its potency was 10 times higher than that of the natural steroid. Intracerebroventricular coadministration experiments with DL-2-amino-5-phosphonovaleric acid, a competitive selective antagonist of the N-methyl-D-aspartate receptor, abolished the memory-enhancing effect of PREGS, but not that of the PREGS enantiomer, evoking enantiomeric selectivity at the N-methyl-D-aspartate receptor and͞or different mechanisms for the promnestic function of the two enantiomers.spatial memory ͉ Y-maze ͉ N-methyl-D-aspartate receptor ͉ 2-amino-5-phosphovaleric acid ͉ rodents S teroids found in the brain, of peripheral origin or locally synthesized (neurosteroids), are known to exert modulatory actions on several functions in the central nervous system. Among them, the neurosteroid pregnenolone sulfate (3␤-hydroxy-5-pregnen-20-one sulfate, PREGS) has been well described as a potent steroidal enhancer of learning and memory processes in rodents (1-6). Of particular interest is the physiological role of PREGS in the hippocampus, which was recently demonstrated for the preservation of age-related spatial memory loss (4). With regards to the mechanism(s) underlying the promnestic action of this endogenous steroid, it is most likely occurring by regulating neurotransmitter receptor function [particularly ␥-aminobutyric acid type A (GABA A ) and N-methyl-D-aspartate (NMDA) receptor activities] in several brain regions (2,3,(7)(8)(9)(10)(11)(12)(13).Particularly relevant to the work here on enantiomeric steroids are the structure-activity data that have demonstrated a marked stereoselectivity for steroid regulation of neurotransmitter receptor function. For example, the endogenous 3␣-hydroxy ring A-reduced steroids, such as the neurosteroid allopregnanolone (3␣-hydroxy-5␣-pregnan-20-one), display potent positive-allosteric modulation of GABA A receptors (14-16) that may explain their anesthetic, anxiolytic, hypnotic, and anticonvulsant effects in animals (17). Conversely, epiallopregnanolone and pregnanolone, the respective 3␤-and 5␤-hydroxy-diastereomers of allopregnanolone (diastereomers having the opposite configuration at only one of multiple chiral centers, in this case at C-3 or C-5, also are known as epimers) are ineffective in potentiating GABA A receptors (18). Cognate evidence for a direct interaction betwe...

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Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 99%

The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?

Akwa

Ladurelle

Covey

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

127

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“…The rapid effect of the sulphated steroid clearly evokes its non-genomic interaction with both the GABA A and / or NMDA receptors and suggests that the learning-induced activation of physiological responses could be enhanced by an increase in neuroactive steroid levels. PREGS also enhanced performances in a spatial recognition memory task after post-acquisition intracerebroventricular infusion (138). Interestingly the active dose, 12 nmol, induced a mild increase in extracellular acetylcholine (ACh) level measured by microdialysis, whereas higher doses (up to 192 nmol) provoked robust increases in ACh levels without behavioral improvement.…”

Section: Neurosteroids and σ Drugs Affect Learning And Memory Processmentioning

confidence: 99%

“…Furthermore, intracerebral microdialysis of PREGS (100 -400 pmol) enhanced in vivo meso-accumbens dopamine release from dopaminergic terminals, and further enhanced morphine-induced dopamine release (137) as well as acetylcholine release from rat hippocampus (138). Recently, Meyer et al (139) reported that PREGS (10 -50 µM), DHEAS (0.1 -1 µM) as well as (+)pentazocine (5 -50 µM) caused a robust and transient enhancement of the frequency and amplitude of AMPAmediated miniature excitatory postsynaptic currents in primary mixed hippocampal cell cultures.…”

Section: Neurosteroids and σ Drugs May Have A Similar Impact On Neuromentioning

confidence: 99%

The Sigma1 Protein as a Target for the Non-genomic Effects of Neuro(active)steroids: Molecular, Physiological, and Behavioral Aspects

2006

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Abstract. Steroids synthesized in the periphery or de novo in the brain, so called 'neurosteroids', exert both genomic and nongenomic actions on neurotransmission systems. Through rapid modulatory effects on neurotransmitter receptors, they influence inhibitory and excitatory neurotransmission. In particular, progesterone derivatives like 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) are positive allosteric modulators of the γ-aminobutyric acid type A (GABA A ) receptor and therefore act as inhibitory steroids, while pregnenolone sulphate (PREGS) and dehydroepiandrosterone sulphate (DHEAS) are negative modulators of the GABA A receptor and positive modulators of the N-methyl-D-aspartate (NMDA) receptor, therefore acting as excitatory neurosteroids. Some steroids also interact with atypical proteins, the sigma (σ) receptors. Recent studies particularly demonstrated that the σ 1 receptor contributes effectively to their pharmacological actions. The present article will review the data demonstrating that the σ 1 receptor binds neurosteroids in physiological conditions. The physiological relevance of this interaction will be analyzed and the impact on physiopathological outcomes in memory and drug addiction will be illustrated. We will particularly highlight, first, the importance of the σ 1 -receptor activation by PREGS and DHEAS which may contribute to their modulatory effect on calcium homeostasis and, second, the importance of the steroid tonus in the pharmacological development of selective σ 1 drugs.

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“…Moreover, one of the behavioral paradigms found to be improved by ginseng and ginseng berry supplementation was that of electroconvulsive shock, which is known to modulate the cholinergic neurotransmitter system, especially within brain areas, such as the hippocampus [110][111][112]. It has also been proposed that ginseng and the ginseng berry enhance the components of cholinergic systems, such as choline acetyl transferase, which is also thought to be important in the formation of memory [113][114][115]. Although there have been a number of studies emphasizing the potential helpful effects of ginseng on cognitive performance in animal models, few epidemiological reports have been performed.…”

Section: Anti-neuro Degeneration Activitymentioning

confidence: 99%

Ginseng Berry, a Promising Anti-Aging Strategy: Recent Opinions on the Biological Effects of a Traditional Korean Ingredient

Seo¹

2016

JARB

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Journal of Advanced Research in Biotechnology Open Access Review Article Introduction: Ginseng and the Ginseng berryGinseng (Panax ginseng) is a popular herbal medicine that has been used in Asia for 5,000 years [1]. Ginseng is classified as fresh, white, or red ginseng, depending on the processing method. As a traditional herb, red ginseng is known as an adaptogen that restores and improves normal well-being. The use of this herbal plant has been widespread throughout the world because of its therapeutic effects. The well-known biochemical and pharmacological effects include anti-cancer [2], anti-fatigue [3], and anti-diabetic effects [4], along with promoting the synthesis of DNA, RNA and proteins [5]. The herb is used as a tea, an extract, or raw directly from powdered root [6]. The representative bioactive compounds are widely considered to begin senosides, which are ginseng-specific saponins [7]. Currently, more than 100 naturally occurring saponins of various types and products of enzymatic conversion have been isolated from the roots, stems, leaves, flowers, berries, and seeds of ginseng. The different parts of ginseng contain distinct ginsenoside profiles, and thus, different parts probably possess different pharmacological effects [8].Recently, many health reports have recommended an increase in fruit intake as part of a healthy dietary pattern [9,10]. These reports allow for various forms of fruit, including fresh, frozen, and dried, as well as juices, and recommend fruits such as oranges, apples, bananas, grapes, raisins, and berries. Whereas berries are known as a good source of potassium or fiber, recent studies suggest that berry fruits are a rich source of many phytochemicals that have a broad spectrum of bioactivity and a positive impact on general health. Several berry fruits, including blackberries, blueberries, cranberries, raspberries, and strawberries, have recently received attention as a result of their effects in vitro and their associations with lowered risks for some chronic diseases, which were found in recent observational research [11,12]. As a perennial herb, ginseng develops flowers and fruits that bloom in its third and fourth year. Unlike the widely used ginseng root, the ginseng berry is preserved for planting and has not been used by general populations. A recent study reported that the ginseng leaf and berry have higher levels of ginsenosides than ginseng root, and their pharmacological activities have also been reported [13]. In this review, we will summarize the research on the role of dietary ginseng berries in delaying aging, as well as evidence suggesting positive biological effects to prevent age-related diseases. Ginseng Berry Bioactive Content and CompositionThe bioactive components of ginseng are triterpene glycosides or saponins, which are commonly regarded as ginsenosides. AbstractA recent effort in the development of new medications and immune modulatory agents is to search for candidates among natural products because they have relatively low toxicities in clinica...

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Pregnenolone sulfate increases hippocampal acetylcholine release and spatial recognition

Cited by 68 publications

References 37 publications

The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?

The synthetic enantiomer of pregnenolone sulfate is very active on memory in rats and mice, even more so than its physiological neurosteroid counterpart: Distinct mechanisms?

The Sigma1 Protein as a Target for the Non-genomic Effects of Neuro(active)steroids: Molecular, Physiological, and Behavioral Aspects

Ginseng Berry, a Promising Anti-Aging Strategy: Recent Opinions on the Biological Effects of a Traditional Korean Ingredient

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