Cognition in aged rhesus monkeys: effect of <scp>DHEA</scp> and correlation with steroidogenic gene expression

Sorwell, Krystina G.; Renner, Lauren; Weiss, Alison R.; Neuringer, Martha; Kohama, Steven G.; Urbanski, Henryk F.

doi:10.1111/gbb.12351

Cited by 13 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Third, the mechanism responsible for the intracrine conversion of DHEA to E 1 and E 2 in the hippocampus may have been less effective in the old animals, a view that is supported by previous studies showing that expression of HSD3B1/2, a gene that encodes a key enzyme in the DHEA- E 2 conversion, itself shows an age-related decrease in the rhesus macaque hippocampus (Sorwell et al, 2012). Taken together, the results help to explain why DHEA supplementation appears to be largely ineffective at improving cognitive function in older monkeys and humans, with most clinical studies failing to demonstrate any significant benefit (e.g., Davis et al, 2011; Panjari & Davis, 2010; Scheffers et al, 2015; Sorwell et al, 2017). …”

Section: Discussionmentioning

confidence: 84%

“…Preliminary tests found this administration paradigm to mimic the youthful circulatory patterns of DHEAS, characterized by daily morning peaks generally in the range of 160 – 400 ng/ml 1–2 hours after DHEA administration (Sorwell et al, 2017). A terminal blood sample was collected at necropsy (at ~ 10: 00 h) from the DHEA-treated animals, as well as from five young adult females (average age = 12.6 ± 0.73 years) and seven DHEA-naïve old females (average age = 23.6 ± 0.62 years).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effect of short-term DHEA supplementation on serum and hippocampal estrogen concentrations in perimenopausal female rhesus macaques

Urbanski

Sorwell

Prókai

et al. 2017

Neurobiology of Aging

View full text Add to dashboard Cite

The hippocampus of rhesus macaques expresses genes that encode key enzymes involved in the intracrine conversion of dehydroepiandrosterone (DHEA) to estradiol. Therefore, it is plausible that supplementary DHEA may enhance hippocampal estradiol concentrations and help to compensate for the marked postmenopausal attenuation of circulating estrogen levels. To test this hypothesis, we used LC-MS/MS to measure estradiol and estrone concentrations in the serum and hippocampus of young and old perimenopausal female rhesus macaques, as well as old perimenopausal females that received daily DHEA (5 mg) oral supplementation for 1 week. Despite lower concentrations of these estrogens in the serum of the older animals, their concentrations in the hippocampus did not show any obvious differences due to age or to DHEA supplementation. The results suggest that de novo estrogen synthesis in the brain may compensate for the perimenopausal loss of estrogens in the circulation even without supplemental DHEA.

show abstract

Section: Discussionmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Effect of short-term DHEA supplementation on serum and hippocampal estrogen concentrations in perimenopausal female rhesus macaques

Urbanski

Sorwell

Prókai

et al. 2017

Neurobiology of Aging

View full text Add to dashboard Cite

show abstract

“…In humans, sulfation of PREG to PregS is catalyzed by SULT2B1a, whereas SULT2B1b preferentially catalyzes the sulfation of 3beta-hydroxysteroids. Non-human primate studies suggest that age-dependent changes in the expression of these enzymes could play a role in age-related changes in cognitive function (96, 97).…”

Section: Synthesis Structure Transport and Cellular Targets Of Neurmentioning

confidence: 99%

Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders

2019

View full text Add to dashboard Cite

Memory dysfunction is a symptomatic feature of many neurologic and neuropsychiatric disorders; however, the basic underlying mechanisms of memory and altered states of circuitry function associated with disorders of memory remain a vast unexplored territory. The initial discovery of endogenous neurosteroids triggered a quest to elucidate their role as neuromodulators in normal and diseased brain function. In this review, based on the perspective of our own research, the advances leading to the discovery of positive and negative neurosteroid allosteric modulators of GABA type-A (GABA A ), NMDA, and non-NMDA type glutamate receptors are brought together in a historical and conceptual framework. We extend the analysis toward a state-of-the art view of how neurosteroid modulation of neural circuitry function may affect memory and memory deficits. By aggregating the results from multiple laboratories using both animal models for disease and human clinical research on neuropsychiatric and age-related neurodegenerative disorders, elements of a circuitry level view begins to emerge. Lastly, the effects of both endogenously active and exogenously administered neurosteroids on neural networks across the life span of women and men point to a possible underlying pharmacological connectome by which these neuromodulators might act to modulate memory across diverse altered states of mind.

show abstract

“…The marmoset was specifically selected for this consortium project as it has several advantages over other laboratory animal species as well as other NHPs for the study of aging and aging-related disorders (Perez-Cruz & de Dios Rodriguez-Callejas, 2023 ; Ross & Salmon, 2019 ; Sukoff Rizzo et al, 2023 ). While the development of cognitive touchscreen batteries has been successfully accomplished in macaques (Loyant et al, 2022 , 2023 ; Sorwell et al, 2017 ; Weed et al, 1999 ; Wither et al, 2020 ), only a few labs have reported the successful integration of multiple touchscreen tasks in marmosets within a battery but with limited studies in aging marmosets (Kangas et al, 2016 ; Sadoun et al, 2019 ; Spinelli et al, 2004 ). This development of a comprehensive testing battery addresses several missed opportunities within the aging research field that may contribute to the lack of translational success from animal models to clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Improving preclinical to clinical translation of cognitive function for aging-related disorders: the utility of comprehensive touchscreen testing batteries in common marmosets

Murai,

Bailey,

Schultz

et al. 2024

Cogn Affect Behav Neurosci

View full text Add to dashboard Cite

Concerns about poor animal to human translation have come increasingly to the fore, in particular with regards to cognitive improvements in rodent models, which have failed to translate to meaningful clinical benefit in humans. This problem has been widely acknowledged, most recently in the field of Alzheimer’s disease, although this issue pervades the spectrum of central nervous system (CNS) disorders, including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. Consequently, recent efforts have focused on improving preclinical to clinical translation by incorporating more clinically analogous outcome measures of cognition, such as touchscreen-based assays, which can be employed across species, and have great potential to minimize the translational gap. For aging-related research, it also is important to incorporate model systems that facilitate the study of the long prodromal phase in which cognitive decline begins to emerge and which is a major limitation of short-lived species, such as laboratory rodents. We posit that to improve translation of cognitive function and dysfunction, nonhuman primate models, which have conserved anatomical and functional organization of the primate brain, are necessary to move the field of translational research forward and to bridge the translational gaps. The present studies describe the establishment of a comprehensive battery of touchscreen-based tasks that capture a spectrum of domains sensitive to detecting aging-related cognitive decline, which will provide the greatest benefit through longitudinal evaluation throughout the prolonged lifespan of the marmoset.

show abstract

Cognition in aged rhesus monkeys: effect of DHEA and correlation with steroidogenic gene expression

Cited by 13 publications

References 44 publications

Effect of short-term DHEA supplementation on serum and hippocampal estrogen concentrations in perimenopausal female rhesus macaques

Effect of short-term DHEA supplementation on serum and hippocampal estrogen concentrations in perimenopausal female rhesus macaques

Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders

Improving preclinical to clinical translation of cognitive function for aging-related disorders: the utility of comprehensive touchscreen testing batteries in common marmosets

Contact Info

Product

Resources

About