Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders

Ratner, Marcia H.; Kumaresan, Vidhya; Farb, David H.

doi:10.3389/fendo.2019.00169

Cited by 97Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsAlzheimer's disease research and treatments

Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders

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Ratner, Marcia H., Kumaresan, Vidhya, Farb, David H.·2019·Frontiers in Endocrinology

DOI 10.3389/fendo.2019.00169PMC PMC6465949

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Abstract

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 (GABAA), 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.

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This prediction is consistent with reported correlations between neurosteroids and a series of neurological disorders, including migraine, postpartum-depression, epilepsy, anxiety, cognitive and psychiatric disorders.
“Such a prediction is consistent with reported correlations between neurosteroids and a series of neurological disorders, including migraine, postpartum-depression, epilepsy, anxiety, cognitive and psychiatric disorders [56,144,145].”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [144]
The Introduction’s Table 2 reports associations involving neurosteroids in Alzheimer’s disease and catamenial epilepsy, and the review discusses depression, schizophrenia, and anxiety disorders. It does not establish the claimed series in full: no passage found addresses migraine, and postpartum depression appears in the References as a brexanolone-treatment study rather than a reported correlation. (LLM, conf=0.86)
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[119]Weaver CE Land MB Malayev AA Purdy RH Richards KG Gibbs TT Farb DH. Geometry and charge determine the pharmacological effects of steroids on the N-methyl-D-aspartate receptor. J Pharmacol Exp Ther. (2000) 293: 747– 54. 10869372

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Additional file 5 of The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice
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Additional file 3 of The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice
Xu, F.-R., Wei, Z.-H., Xu, X.-X., Zhang, X.-G., Wei, C.-J., Qi, X.-M., Li, Y.-H., Gao, X.-L., & Wu, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26651022
Additional file 4 of The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice
Xu, F.-R., Wei, Z.-H., Xu, X.-X., Zhang, X.-G., Wei, C.-J., Qi, X.-M., Li, Y.-H., Gao, X.-L., & Wu, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26651025
Additional file 1 of The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice
Xu, F.-R., Wei, Z.-H., Xu, X.-X., Zhang, X.-G., Wei, C.-J., Qi, X.-M., Li, Y.-H., Gao, X.-L., & Wu, Y. (2023) · Figshare · doi:10.6084/m9.figshare.24770381
Additional file 1 of Pharmacological modulation of TSPO in microglia/macrophages and neurons in a chronic neurodegenerative model of prion disease
Vicente‐Rodríguez, M., Mancuso, R., Peris-Yague, A., Simmons, C., Gómez‐Nicola, D., Perry, V. H., Turkheimer, F., Lovestone, S., Parker, C. A., & Cash, D. (2024) · Figshare · doi:10.6084/m9.figshare.26581280
Additional file 2 of Altered immune phenotype and DNA methylation in panic disorder
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Additional file 1 of Comparison of pregnenolone sulfate, pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study
Rustichelli, C., Bellei, E., Bergamini, S., Monari, E., Lo Castro, F., Baraldi, C., Tomasi, A., & Ferrari, A. (2021) · Figshare · doi:10.6084/m9.figshare.14302929
Additional file 2 of The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice
Xu, F.-R., Wei, Z.-H., Xu, X.-X., Zhang, X.-G., Wei, C.-J., Qi, X.-M., Li, Y.-H., Gao, X.-L., & Wu, Y. (2024) · Figshare · doi:10.6084/m9.figshare.24770687
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Site and mechanism of BK channel inhibition and cerebral artery constriction by pregnenolone
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Mechanistic Insights into Adaptive Binding of Vitamins and Hormones at Hotspot-Enriched Interfaces of the Synaptotagmin 1 C2AB DomainPreprint
Hazra, S., Tiwary, B. K., Chaudhuri, A. G., & Chakrabarti, N. B. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.18.760018

Authors: Ratner, M. H., Kumaresan, V., & Farb, D. H.
Affiliations: Boston University (US)
Corresponding author: Farb, David H.
ORCID: Ratner, Marcia H.
Kumaresan, Vidhya
Farb, David H.
Venue: Frontiers in Endocrinology
Publisher: Frontiers Media SA
Published: 2019-04-09
Volume: 10
Pages: 169-169
ISSN: 1664-2392 (ISSN-L)
DOI: 10.3389/fendo.2019.00169
PMC: PMC6465949
OpenAlex: W2939309394
Cited by: 96
References: 412
Citations by year: 2026: 5 · 2025: 4 · 2024: 14 · 2023: 16 · 2022: 18 · 2021: 22 · 2020: 15 · 2019: 1 · 2018: 1
FWCI: 1.86
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Endocrinology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute on Aging (R21AG056947)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: neurosteroids, memory, GABAA receptor, NMDA receptor, non-NMDA receptors, allosteric modulation, neuromodulation, neural circuits, memory impairment, neuropsychiatric disorders, neurodegenerative diseases, sex differences

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Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders

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