Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: Mechanism of action and relevance to psychiatric disorders

Pérez-Neri, Iván; Montes, Sergio; Ojeda-López, Carmen; Ramı́rez-Bermúdez, Jesús; Rı́os, Camilo

doi:10.1016/j.pnpbp.2007.12.001

Cited by 74 publications

(51 citation statements)

References 135 publications

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“…However, both stimulatory and inhibitory effects have been reported under different experimental conditions. In mice models fed with DHEA supplemented diet, increased or decreased serotonin synthesis and turnover were noted at different doses and in different brain regions (42). The significant inverse correlation between urine 5-HIAA and DHEA/ DHEAS in the present study may suggest increased brain serotonin activity.…”

Section: Discussionsupporting

confidence: 56%

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Effect of Exposure to Selective Serotonin Reuptake Inhibitors In Utero on Fetal Growth: Potential Role for the IGF-I and HPA Axes

et al. 2009

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ABSTRACT:To investigate the possible effect of fetal exposure to selective serotonin reuptake inhibitors (SSRIs) on somatic growth and on hormones of the hypothalamic-pituitary-adrenal (HPA) and insulin-like growth factor (IGF)-I axes, we compared the anthropometric parameters and hormonal profile of 21 SSRI-exposed infants and 20 matched controls. The SSRI group was characterized by lower crown-heel length (p Ͻ 0.01), smaller head circumference (p ϭ 0.08), and higher percentage of infants with birth weight, birth length, and head circumference below the 10th percentile (p Ͻ 0.045, p ϭ 0.08, p Ͻ 0.04, respectively), in addition to a significantly lower cord blood level of cortisol (p Ͻ 0.03) and higher level of thyroidstimulating hormone (TSH) (p Ͻ 0.004). Infants exposed to citalopram had a lower cord blood IGF-I level than infants exposed to paroxetine (p Ͻ 0.001) and controls (p Ͻ 0.003). Placental IGF-I receptor (IGF-IR) expression was significantly higher in the SSRI group than in controls (p Ͻ 0.01). Urine 5-hydroxyindoleacetic acid T he reported prevalence of depression in women of childbearing age and during pregnancy ranges from 10 to 15% (1-3). Treatment usually consists of selective serotonin reuptake inhibitors (SSRIs), especially citalopram, fluoxetine, paroxetine, sertraline, and fluvoxamine. However, their safety for the fetus has not been fully established. Findings regarding major congenital malformations are conflicting (4 -6). Several recent studies suggest that although individual SSRIs may confer an increased risk of some specific birth defects (as expressed by the odds ratios), there is only a slight effect on absolute risk (7-9). Others observed that third-trimester intake of SSRIs accounts for symptoms of poor neonatal adaptation (10 -14) and, consequently, higher-than-normal rates of admission to neonatal special care and intensive care units (10,15). According to a 2005 literature review, SSRI exposure is associated with an overall risk ratio of 3.0 (95% CI, 2.0 -4.4) for neonatal behavioral syndrome (12); one study also reported an alarming complication of persistent infantile pulmonary hypertension (16). It remains unclear, however, if these symptoms are a manifestation of abrupt drug withdrawal at delivery or of serotonergic overstimulation during pregnancy. Studies have shown that maternal SSRI intake during pregnancy induced a significant reduction in cord blood levels of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) (1,17). Laine et al.(1) reported that the cord blood 5-HIAA level was inversely and significantly correlated with the clinical serotonergic symptom score and attributed this finding to the increase in central nervous system (CNS) serotonin activity.The question of whether in utero exposure to SSRIs affects birth weight and/or length and head circumference is also unresolved. Some studies noted decreased values of these parameters (18 -21), whereas others did not (1,2,5). Growth attenuation accompanied by impaired growth hormone (GH) secretion was also reported in f...

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Section: Discussionsupporting

confidence: 56%

“…3) as well as the inverse association between urine 5-HIAA and DHEA/DHEAS have never been reported. DHEA and its sulfate ester, DHEAS, act as modulators of several neurotransmitter systems including serotonin (42). However, both stimulatory and inhibitory effects have been reported under different experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Effect of Exposure to Selective Serotonin Reuptake Inhibitors In Utero on Fetal Growth: Potential Role for the IGF-I and HPA Axes

et al. 2009

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“…The Finnegan score, as a measure of gross CNS and respiratory function, positively correlated with placental insulin-like growth factor-1 receptor expression and cord cortisol concentrations. Finnegan scores also correlated with dehydroepiandrosterone and its metabolite, dehydroepiandrosterone sulfate, which play an important role in regulating serotonin, dopamine, glutamate, and GABA neurotransmitter systems through modulation of receptor activation (Pérez-Neri et al, 2008). These correlations were only observed in SSRI-exposed groups and not healthy control groups (Davidson et al, 2009).…”

Section: F Monoamine and Hormone Studiesmentioning

confidence: 92%

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

2014

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“…DHEAS modulates synaptic transmission and so has a variety of effects in the central nervous system (Pérez-Neri et al, 2008). Up to now, the physiological effect of DHEAS, notably concerning memory and learning ability, has mainly been investigated in the hippocampus (Dubrovsky, 2005;Steffensen et al, 2006).…”

Section: Downloaded Frommentioning

confidence: 99%

Organic Anion Transporter 3 Mediates the Efflux Transport of an Amphipathic Organic Anion, Dehydroepiandrosterone Sulfate, across the Blood-Brain Barrier in Mice

Miyajima

Kusuhara²,

Fujishima³

et al. 2011

Drug Metab Dispos

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ABSTRACT:The present study investigated the efflux transport systems of organic anions across the blood-brain barrier (BBB) using dehydroepiandrosterone sulfate (DHEAS) as a probe. The elimination of DHEAS from the brain after microinjection into the cerebral cortex was characterized in wild-type mice and mice with deficiency of well characterized organic anion transporters, organic aniontransporting polypeptide 1a4 (Oatp1a4)/Slco1a4 and organic anion transporter 3 (Oat3)/Slc22a8, at the BBB. The saturable efflux of DHEAS from the brain was completely inhibited by probenecid, benzylpenicillin, and estrone-3-sulfate and moderately inhibited by taurocholate and p-aminohippurate (50-57%). Uptake of DHEAS and estrone-3-sulfate was greater in murine Oat3 cRNA-injected oocytes than that in water-injected oocytes. Efflux of these compounds from the brain was significantly delayed in Oat3(؊/؊) mice compared with that in wild-type mice, indicating that indeed Oat3 is functionally important in vivo. Furthermore, probenecid and taurocholate inhibited DHEAS efflux completely in Oat3(؊/؊) mice. Contrary to the past report in rats that suggested involvement of Oatp1a4, specific uptake of DHEAS and estrone-3-sulfate by murine Oatp1a4 was not detected in vitro, and efflux of both compounds from the brain was not altered in Oatp1a4(؊/؊) mice. There was no significant difference in the uptake of DHEAS by brain slices prepared from wild-type, Oatp1a4(؊/؊), and Oat3(؊/؊) mice. Taken together, these results suggest that Oat3 plays a significant role in the efflux of steroid conjugates across the BBB in mice and that the BBB also expresses other unknown organic anion transporters for the efflux of DHEAS. Transport mechanisms of organic anions at the BBB are far more diverse than they were assumed to be.

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Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: Mechanism of action and relevance to psychiatric disorders

Cited by 74 publications

References 135 publications

Effect of Exposure to Selective Serotonin Reuptake Inhibitors In Utero on Fetal Growth: Potential Role for the IGF-I and HPA Axes

Effect of Exposure to Selective Serotonin Reuptake Inhibitors In Utero on Fetal Growth: Potential Role for the IGF-I and HPA Axes

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

Organic Anion Transporter 3 Mediates the Efflux Transport of an Amphipathic Organic Anion, Dehydroepiandrosterone Sulfate, across the Blood-Brain Barrier in Mice

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