Dehydroepiandrosterone, Its Sulfate and Cognitive Functions

Menezes, Karina Junqueira de; Peixoto, Clayton; Nardi, Antônio Egídio; Carta, Mauro Giovanni; Machado, Sérgio; Veras, André Barciela

doi:10.2174/1745017901612010024

Cited by 33 publications

(28 citation statements)

References 52 publications

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“…DHEA is available as an over-the-counter nutritional supplement with a range of putative beneficial effects (on aging, neurocognitive impairments, cardiovascular disease, immune, and allergic disorders) albeit none are specific indications for its use at present (Castanho et al, 2014;de Menezes et al, 2016;Dillon, 2005). A previous study suggested that through DHEA's action on NFjB signaling, it could enhance a Th2 phenotype in activation lymphocytes (Du, Khalil & Sriram, 2001;Sun, Yang, Zang, & Wu, 2010).…”

Section: Discussionmentioning

confidence: 99%

Suppressed oligodendrocyte steroidogenesis in multiple sclerosis: Implications for regulation of neuroinflammation

Boghozian

McKenzie

Saito

et al. 2017

Glia

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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Neurosteroids are reported to exert anti-inflammatory effects in several neurological disorders. We investigated the expression and actions of the neurosteroid, dehydroepiandrosterone (DHEA), and its more stable 3β-sulphated ester, DHEA-S, in MS and associated experimental models. CNS tissues from patients with MS and animals with experimental autoimmune encephalomyelitis (EAE) displayed reduced DHEA concentrations, accompanied by diminished expression of the DHEA-synthesizing enzyme CYP17A1 in oligodendrocytes (ODCs), in association with increased expression of inflammatory genes including interferon (IFN)-γ and interleukin (IL)-1β. CYP17A1 was expressed variably in different human neural cell types but IFN-γ exposure selectively reduced CYP17A1 detection in ODCs. DHEA-S treatment reduced IL-1β and -6 release from activated human myeloid cells with minimal effect on lymphocyte viability. Animals with EAE receiving DHEA-S treatment showed reduced Il1b and Ifng transcript levels in spinal cord compared to vehicle-treated animals with EAE. DHEA-S treatment also preserved myelin basic protein immunoreactivity and reduced axonal loss in animals with EAE, relative to vehicle-treated EAE animals. Neurobehavioral deficits were reduced in DHEA-S-treated EAE animals compared with vehicle-treated animals with EAE. Thus, CYP17A1 expression in ODCs and its product DHEA were downregulated in the CNS during inflammatory demyelination while DHEA-S provision suppressed neuroinflammation, demyelination, and axonal injury that was evident as improved neurobehavioral performance. These findings indicate that DHEA production is an immunoregulatory pathway within the CNS and its restoration represents a novel treatment approach for neuroinflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Suppressed oligodendrocyte steroidogenesis in multiple sclerosis: Implications for regulation of neuroinflammation

Boghozian

McKenzie

Saito

et al. 2017

Glia

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“…Although a decrease in CD ratios throughout the day have been associated with a decrease in personality disorder symptoms in adult women, lower CD ratios may be associated with less adaptive coping skills and resilience in children . There is also evidence that higher DHEA levels may optimise working memory and executive function, whereas higher cortisol levels may increase distractibility and as a result, impair executive function . Similarly, DHEA may have a beneficial effect on verbal abilities, particularly in women, whereas higher cortisol levels have been associated with decreased performance on tests of verbal memory and learning .…”

Section: Introductionmentioning

confidence: 99%

“…There is also evidence that higher DHEA levels may optimise working memory and executive function, whereas higher cortisol levels may increase distractibility and as a result, impair executive function . Similarly, DHEA may have a beneficial effect on verbal abilities, particularly in women, whereas higher cortisol levels have been associated with decreased performance on tests of verbal memory and learning . Higher CD ratios have also been associated with lower visuo‐spatial memory performance in both men; conversely, administration of DHEA improved visuo‐spatial abilities in women at a given cortisol level .…”

Section: Introductionmentioning

confidence: 99%

Sex‐specific contribution of DHEA‐cortisol ratio to prefrontal‐hippocampal structural development, cognitive abilities and personality traits

Farooqi

Scotti

et al. 2019

J Neuroendocrinology

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Although dehydroepiandrosterone (DHEA) may exert neuroprotective effects in the developing brain, prolonged or excessive elevations in cortisol may exert neurotoxic effects. The ratio between DHEA and cortisol (DC ratio) has been linked to internalising and externalising disorders, as well as cognitive performance, supporting the clinical relevance of this hormonal ratio during development. However, the brain mechanisms by which these effects may be mediated have not yet been identified.Furthermore, although there is evidence that the effects of cortisol in the central nervous system may be sexually dimorphic in humans, the opposite is true for DHEA, with human studies showing no sex-specific associations in cortical thickness, cortico-amygdalar or cortico-hippocampal structural covariance. Therefore, it remains unclear whether sex moderates the developmental associations between DC ratio, brain structure, cognition and behaviour. In the present study, we examined the associations between DC ratio, structural covariance of the hippocampus with

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“…Reports of DHEA administration in adults also outline beneficial effects on cognition overall, with a certain specificity for working memory and attention (Alhaj et al, 2006; Davis et al, 2008; de Menezes et al, 2016; do Vale et al, 2014). Recent findings from our group support some of these ‘pro-cognition’ effects of DHEA by showing that DHEA ameliorates visual attention processes by shaping amygdala-dependent cortical plasticity from childhood to young adulthood (Nguyen et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…In turn, this DHEA-related structural covariance was related to improved performance on tests of visual awareness, visuo-motor dexterity and general level of attention (Nguyen et al, 2016). Still, not all studies are consistent with regards to the association between DHEA and different aspects of declarative, episodic and working memory, and sex and age differences in the cognitive effects of DHEA have been reported (de Menezes et al, 2016). In addition, there have been no studies, to our knowledge, examining the relationship between DHEA, brain structure, and working memory during development.…”

Section: Introductionmentioning

confidence: 99%

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development

Nguyen

Lew

et al. 2017

Psychoneuroendocrinology

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Existing studies suggest that dehydroepiandrosterone (DHEA) may be important for human brain development and cognition. For example, molecular studies have hinted at the critical role of DHEA in enhancing brain plasticity. Studies of human brain development also support the notion that DHEA is involved in preserving cortical plasticity. Further, some, though not all, studies show that DHEA administration may lead to improvements in working memory in adults. Yet these findings remain limited by an incomplete understanding of the specific neuroanatomical mechanisms through which DHEA may impact the CNS during development. Here we examined associations between DHEA, cortico-hippocampal structural covariance, and working memory (216 participants [female=123], age range 6–22 years old, mean age: 13.6 +/−3.6 years, each followed for a maximum of 3 visits over the course of 4 years). In addition to administering performance-based, spatial working memory tests to these children, we also collected ecological, parent ratings of working memory in everyday situations. We found that increasingly higher DHEA levels were associated with a shift toward positive insular-hippocampal and occipito-hippocampal structural covariance. In turn, DHEA-related insular-hippocampal covariance was associated with lower spatial working memory but higher overall working memory as measured by the ecological parent ratings. Taken together with previous research, these results support the hypothesis that DHEA may optimize cortical functions related to general attentional and working memory processes, but impair the development of bottom-up, hippocampal-to-cortical connections, resulting in impaired encoding of spatial cues.

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Dehydroepiandrosterone, Its Sulfate and Cognitive Functions

Cited by 33 publications

References 52 publications

Suppressed oligodendrocyte steroidogenesis in multiple sclerosis: Implications for regulation of neuroinflammation

Suppressed oligodendrocyte steroidogenesis in multiple sclerosis: Implications for regulation of neuroinflammation

Sex‐specific contribution of DHEA‐cortisol ratio to prefrontal‐hippocampal structural development, cognitive abilities and personality traits

Dehydroepiandrosterone impacts working memory by shaping cortico-hippocampal structural covariance during development

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