Gender and Neurosteroids: Implications for Brain Function, Neuroplasticity and Rehabilitation
Open accessAbstract
Neurosteroids are synthesized de novo in the nervous system; they mainly moderate neuronal excitability, and reach target cells via the extracellular pathway. The synthesis of neurosteroids occurs in peripheral tissues such as gonads tissues, liver, and skin; then, because of their high lipophilia, they cross the blood–brain barrier and are stored in the brain structure. Neurosteroidogenesis occurs in brain regions such as the cortex, hippocampus, and amygdala by enzymes necessary for the in situ synthesis of progesterone from cholesterol. Neurosteroids could be considered the main players in both sexual steroid-induced hippocampal synaptic plasticity and normal transmission in the hippocampus. Moreover, they show a double function of increasing spine density and enhancing long term potentiation, and have been related to the memory-enhancing effects of sexual steroids. Estrogen and progesterone affect neuronal plasticity differently in males and females, especially regarding changes in the structure and function of neurons in different regions of the brain. Estradiol administration in postmenopausal women allowed for improving cognitive performance, and the combination with aerobic motor exercise seems to enhance this effect. The paired association between rehabilitation and neurosteroids treatment could provide a boosting effect in order to promote neuroplasticity and therefore functional recovery in neurological patients. The aim of this review is to investigate the mechanisms of action of neurosteroids as well as their sex-dependent differences in brain function and their role in neuroplasticity and rehabilitation.
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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 [145]
Sections 5.1–5.3 link neurosteroids with epilepsy, migraine, anxiety, cognitive impairment, depression, and neuropsychiatric disorders. Section 5.3 discusses depression generally, but neither it nor the passages retrieved for “postpartum depression” identifies postpartum depression specifically. (LLM, conf=0.88)
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Reduced steroidogenesis in patients with PCDH 19‐female limited epilepsy
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Steroid Effects on Glial Cells
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Endocrine regulation of estrogen synthesis in the hippocampus?
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Localization of P450scc and 5α-reductase type-2 in the cerebellum of fetal and newborn sheep
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Darbra, S., & Pallarés, M. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.08.020 · Cited by 35 · see citing works
Gizerian, S. S., Morrow, A. L., Lieberman, J. A., & Grobin, A. C. (2004) · Brain Research · doi:10.1016/j.brainres.2004.03.049 · Cited by 31 · see citing works
Benarroch, E. E. (2007) · Neurology · doi:10.1212/01.wnl.0000257836.09570.e1 · Cited by 31 · see citing works
SAKATA, K., Tokue, A., & Kawai, N. (2000) · The Journal of Urology · doi:10.1016/s0022-5347(05)67773-7 · Cited by 31 · see citing works
Influence of neurosteroids on the pathogenesis of multiple sclerosis
Leitner, H. (2010) · Medical Hypotheses · doi:10.1016/j.mehy.2010.02.028 · Cited by 28 · see citing works
Sex Differences in Long-Term Consequences of Prenatal Diazepam Exposure
Kellogg, C. K. (1999) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(99)00137-9 · Cited by 28 · see citing works
Finasteride inhibited brain dopaminergic system and open‐field behaviors in adolescent male rats
Li, L., Kang, Y., Ji, X., Li, Y., Li, S., Zhang, X., Cui, H., & Shi, G. (2017) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12781 · Cited by 28 · see citing works
Gatta, E., Camussi, D., Auta, J., Guidotti, A., & Pandey, S. C. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108299 · Cited by 28 · see citing works
Prat, A., Behrendt, M., Marcinkiewicz, E., Boridy, S., Sairam, R., Seidah, N. G., & Maysinger, D. (2011) · Journal of Aging Research · doi:10.4061/2011/251517 · Cited by 27 · see citing works
Migraine and cluster headache show impaired neurosteroids patterns
Koverech, A., Cicione, C., Lionetto, L., Maestri, M., Passariello, F., Sabbatini, E., Capi, M., Marco, C. M. D., Guglielmetti, M., Negro, A., et al. (2019) · The Journal of Headache and Pain · doi:10.1186/s10194-019-1005-0 · Cited by 25 · see citing works
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Investigational small molecules in phase II clinical trials for the treatment of epilepsy
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Induction of Neuroplasticity by Transcranial Direct Current Stimulation.
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Neural sex steroids and hippocampal synaptic plasticity
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Gender differences in susceptibility to schizophrenia: Potential implication of neurosteroids
Huang, Y., Hung, C., Lin, P., Lee, Y., Wu, C., Hsu, S., Chen, C.-C., Chong, M., Lin, C., & Wang, L. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.06.017 · Cited by 16 · see citing works
Transient expression of S-100β immunostaining in developing thalamus and somatosensory cortex of rat
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Protocadherin 19 Clustering Epilepsy and Neurosteroids: Opportunities for Intervention
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Sex‐dependent responsiveness of hippocampal neurons to sex neurosteroids: A role of Arc/Arg3.1
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Synthesis and impact of neuroestradiol on hippocampal neuronal networks
Azcoitia, Í., Hernández‐Vivanco, A., Cano-Adamuz, N., & Méndez, P. (2022) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2022.100335 · Cited by 5 · see citing works
Sex neurosteroidogenesis and hippocampal network maintenance
Brunne, B., & Rune, G. M. (2022) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2022.100316 · Cited by 3 · see citing works
Flagged first, then by citations
1 of the 126 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
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Transcriptomic and metabolomic changes might predict frailty in SAMP8 mice
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Reduced Levels of Neurosteroids in Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients
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The molecular fundamentals of neurorehabilitation and their modulation by thyroid hormones
Kamyshna, I. I., Pavlovych, L., Pankiv, V. І., Khodorovska, A. A., Bilous, O., & Kamyshnyi, O. (2024) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.20.2.2024.1374 · Cited by 3 · see citing works
Liu, H., Zhang, Y.-J., & Zhang, W. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1418455 · Cited by 3 · see citing works
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Neurosteroids and Translocator Protein (TSPO) in neuroinflammation
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- Authors
- Raciti, L., Formica, C., Raciti, G., Quartarone, A., & Calabrò, R. S.
- Affiliations
- Centro Neurolesi Bonino Pulejo (IT)
- Corresponding author
- Formica, Caterina
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2023-03-01
- Volume
- 24
- Issue
- 5
- Pages
- 4758
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC10003563
- OpenAlex
- W4322771326
- Cited by
- 33
- References
- 126
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 17 · 2023: 2
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- neurosteroids, sex differences, neurosteroidogenesis, hippocampal synaptic plasticity, long-term potentiation, estrogen, progesterone, estradiol, postmenopausal women, cognitive performance, aerobic exercise, neuroplasticity, rehabilitation, neurological recovery, blood-brain barrier, neuronal excitability
- MeSH terms
- Neurosteroids, Brain, Female, Humans, Male, Neuronal Plasticity, Neurons, Progesterone, Steroids
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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