Dehydroepiandrosterone increases synaptosomal glutamate release and improves the performance in inhibitory avoidance task

Lhullier, Francisco Luiz Rodrigues; Nicolaidis, Rafael; Riera, Neusa Gruschinske; Cipriani, Franciele; Junqueira, Débora; Dahm, K.; Brusque, Ana Maria; Souza, Diogo O.

doi:10.1016/j.pbb.2003.12.015

Cited by 24 publications

(9 citation statements)

References 48 publications

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“…DHEA/S has been shown to antagonize the androgen receptor and agonize estrogen receptor β; thus, it may exert some of the same actions as estradiol (Chen et al 2005). Also, DHEA/S may affect synaptic plasticity in the hippocampus through antagonism of the GABA A receptor (Majewska 1992), facilitating long-term potentiation via NMDA agonism (Mellon and Griffin 2002; Chen et al 2006), and enhancing glutamate release during learning (Lhullier et al 2004). As mentioned earlier, DHEA/S significantly protects the CNS against the effects of cortisol by attenuating its suppression of neurogenesis (Karishma and Herbert 2002).…”

Section: Effects Of Dhea/s and Neurosteroidogenesis In Rodentsmentioning

confidence: 99%

Dehydroepiandrosterone and age-related cognitive decline

Sorwell

Urbanski

2009

AGE

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In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.

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Section: Effects Of Dhea/s and Neurosteroidogenesis In Rodentsmentioning

confidence: 99%

Dehydroepiandrosterone and age-related cognitive decline

Sorwell

Urbanski

2009

AGE

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“…DHEA and DHEAS indirectly stimulate NMDA receptor activity, and DHEA has been reported to potentiate glutamate release both in vitro and in vivo (Lhullier et al, 2004). Administration of DHEA may produce beneficial effects by increasing glutamatergic transmission via increasing activity of the NMDA receptor.…”

Section: Other Neurotransmitter Systems Affected By Altered Neuroactimentioning

confidence: 99%

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

et al. 2007

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1. Neuroactive steroids are steroid hormones that exert rapid, nongenomic effects at ligand-gated ion channels. There is increasing awareness of the possible role of these steroids in the pathology and manifestation of symptoms of psychiatric disorders. The aim of this paper is to review the current knowledge of neuroactive steroid functioning in the central nervous system, and to assess the role of neuroactive steroids in the pathophysiology and treatment of symptoms of schizophrenia, depression, and anxiety disorders. Particular emphasis will be placed on GABAA receptor modulation, given the extensive knowledge of the interactions between this receptor complex, neuroactive steroids, and psychiatric illness. 2. A brief description of neuroactive steroid metabolism is followed by a discussion of the interactions of neuroactive steroids with acute and chronic stress and the HPA axis. Preclinical and clinical studies related to psychiatric disorders that have been conducted on neuroactive steroids are also described. 3. Plasma concentrations of some neuroactive steroids are altered in individuals suffering from schizophrenia, depression, or anxiety disorders compared to values in healthy controls. Some drugs used to treat these disorders have been reported to alter plasma and brain concentrations in clinical and preclinical studies, respectively. 4. Further research is warranted into the role of neuroactive steroids in the pathophysiology of psychiatric illnesses and the possible role of these steroids in the successful treatment of these disorders.

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“…Neurosteroids exert multiple effects in the central nervous system mediated through its nongenomic actions on several neurotransmitter systems, such as gamma-aminobutyric acid (GABA A ), N-methyl-D-aspartate (NMDA), and sigma receptors (Majewska, 1992;Debonnel et al, 1996;Wen et al, 2001), modulating neuronal excitability and plasticity, as well as presenting neuroprotective properties (Kimonides et al, 1998;Cardounel et al, 1999;Wolf and Kirschbaum, 1999;Lhullier et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

Ritsner

Gibel

Maayan

et al. 2005

Neuropsychopharmacol

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Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together abbreviated DHEA(S)) exert multiple effects in the central nervous system, and may be involved in the pathophysiological processes in schizophrenia. This prospective study aimed to investigate whether serum cortisol/DHEA(S) molar ratios are associated with response to antipsychotic treatment during the exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with acute exacerbation. The patients were treated with stable doses of antipsychotic agents up to 2 weeks prior to entering the study and for the 4-week duration of the study after which they were classified as either responders or nonresponders to treatment. Findings suggest that responders had significantly higher serum cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These differences remained significant at three time points controlling for gender, age, severity of symptoms and emotional distress, benzodiazepines, type or dosage of antipsychotic agents, and background variables. The logistic regression model shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment. No significant canonical correlations were observed between changes from baseline through end-of-study in hormonal values and severity of symptoms and emotional distress among responders and nonresponders. Thus, these data provide evidence that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of biological mechanisms that are involved in responsivity of schizophrenia patients to antipsychotic treatment.

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Dehydroepiandrosterone increases synaptosomal glutamate release and improves the performance in inhibitory avoidance task

Cited by 24 publications

References 48 publications

Dehydroepiandrosterone and age-related cognitive decline

Dehydroepiandrosterone and age-related cognitive decline

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

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