The Impact of Estrogen and Estrogen-Like Molecules in Neurogenesis and Neurodegeneration: Beneﬁcial or Harmful?

Frontiers in Cellular Neuroscience, 2021 · DOI: 10.3389/fncel.2021.636176 · Published: March 8, 2021

Simple Explanation

Estrogens and estrogen-like molecules can modify the biology of several cell types, including those in the central nervous system. They interact with estrogen receptors to modulate cell proliferation, differentiation, and survival. Estrogens can protect nerve cells by acting as antioxidants, repairing DNA, and promoting the expression of growth factors. These actions influence the balance between neural stem cell proliferation and differentiation. Given the widespread use of estrogen-based therapies and the presence of estrogen-like molecules in the environment, understanding their effects on cell biology and tissue balance is important for human health.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Estrogens, including estradiol, promote survival in neurons subjected to stress conditions and may counteract aging-associated cognitive decline and prevent Alzheimer’s disease.
2
Estrogen receptors are expressed in neural stem/progenitor cells, and estrogen stimulation can increase their proliferative activity and influence their differentiation into neurons or oligodendrocytes.
3
Xenoestrogens like bisphenol-A can disrupt the neurogenic process, affecting the proliferation and differentiation balance of neural stem/progenitor cells and neuronal maturation, sometimes leading to harmful effects in the CNS.

Research Summary

The review summarizes the roles of endogenous estrogens, estrogen-based therapies, and estrogen-like molecules on brain homeostasis, especially regarding neurogenesis, gliogenesis, and neuroprotection. Estrogens' neuroprotective functions involve antioxidant activity, DNA repair, growth factor synthesis, synaptic plasticity, and cerebral blood flow, which are crucial for neuronal survival and preventing cognitive decline. Phytoestrogens and their metabolites may offer a promising approach to prevent neurodegenerative disorders, while xenoestrogens can disrupt estrogen-mediated signaling pathways, with potential consequences for chronic exposure.

Practical Implications

Therapeutic potential of phytoestrogens

Phytoestrogens and their metabolites could be developed as preventive measures against neurodegenerative diseases, mimicking the benefits of endogenous estrogens.

HRT benefits for post-menopausal women

Hormone replacement therapy could be considered as a neuroprotective factor for post-menopausal women, particularly in preventing Alzheimer's disease.

Public health concern about xenoestrogens

Public health should address the potential risks of chronic exposure to xenoestrogens, especially bisphenol-A, and its impact on neurological health.

Study Limitations

1
Most in vitro studies evaluate phytoestrogens in isolation, neglecting the combined effects of multiple molecules.
2
Individual differences in microbiome composition can influence the metabolism and effects of phytoestrogens.
3
The relatively low biological potency and affinity of xenoestrogens for classical and non-classical ERs may generate some controversy.

Your Feedback

Was this summary helpful?

Back to Endocrinology