About this Research Topic
Neuroactive steroids, including hormonal steroids, neurosteroids, and synthetic steroids, target neurons and glial cells, exerting neurotrophic and neuroprotective effects.
This proposal aims to summarize the current understanding of the role of neuroactive steroids in brain health, cognition, and neurodegenerative diseases, with a focus on estrogens and aromatase-mediated neuroprotection.
Estrogens, such as estradiol, play a vital role in maintaining neural function beyond their involvement in neuroendocrine regulation and reproductive behaviors.Clinical evidence suggests that estrogen exposure reduces the risk, delays the onset, and slows the progression of Alzheimer's disease, schizophrenia, and enhances recovery from neurological injuries like stroke.
Recent studies highlight the brain's ability to upregulate estrogen synthesis and estrogen receptor expression at sites of injury, indicating a direct protective role of estrogen. This protection encompasses various mechanisms, including altered cell survival, axonal sprouting, enhanced synaptic transmission, enhanced neurogenesis, and modulation of estrogen-responsive genes involved in apoptosis and axonal regeneration. While some neuronal populations may be affected negatively by estradiol exposure, the potential clinical benefits of estrogen treatment for enhancing cognitive function may outweigh the associated risks.
The aromatase enzyme (coded by the CYP19A1 gene) responsible for estrogen synthesis is expressed widely in the human brain, specifically in excitatory and inhibitory neurons, astrocytes, and other cell types. Studies in animal models indicate that brain aromatization of androgens to estrogens plays a crucial role in regulating various brain functions, influencing sensory integration, body homeostasis, social behavior, cognition, language, and integrative functions. Understanding the consequences of aromatase expression in the human brain is vital, particularly considering its relevance to the manifestations of neurodegenerative conditions and sex-specific disorders like autism spectrum disorders, major depressive disorder, multiple sclerosis, stroke, and Alzheimer's disease.
Understanding the roles and mechanisms of action of these steroids opens opportunities for novel therapeutic options for psychiatric disorders, cognition enhancement, and neurodegenerative diseases. Continued research into the complexities of neuroactive steroids, particularly with a focus on aromatase expression in the human brain, will provide valuable insights for future clinical applications, informing personalized treatments and improving patient outcomes.
With this collection, we aim to gather manuscripts investigating the role of estrogens and their potential therapeutic approaches, by focusing on the following topics:
- Impact of female hormones on the brain: neuroimaging studies to study.the neurodegenerative disease progress such as Alzheimer’s Disease and ischemic stroke;
- the role of estrogens, their interaction with neurotrophins and their receptors, focuses on optimizing ligands and doses for clinical use;
- exploring interactions with survival and regeneration-promoting factors, and examining estrogenic effects on neuronal replenishment and neural stem cells' phenotypic choices;
- explore the intricate mechanisms underlying the neuroprotective effects of neuroactive steroids, including the interaction between insulin-like growth factor-1 (IGF-1) and estrogens in neuroprotection, highlighting their role as potential therapeutic options;
- a comprehensive exploration of the expression of female hormones and aromatase in the brain by neuroimaging studies and their impact on various neurological conditions to pave the way for future clinical applications and therapeutic implications.
Keywords: neuroactive steroids, estrogens, aromatases, neuroprotection, therapeutics
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.