Brain-Derived Estrogen and Neurological Disorders

Darrell W. Brann, Yujiao Lu, Jing Wang, Gangadhara R. Sareddy, Uday P. Pratap, Quanguang Zhang, Rajeshwar R. Tekmal, Ratna K. Vadlamudi

Research output: Contribution to journalReview articlepeer-review

Abstract

Astrocytes and neurons in the male and female brains produce the neurosteroid brain-derived 17β-estradiol (BDE2) from androgen precursors. In this review, we discuss evidence that suggest BDE2 has a role in a number of neurological conditions, such as focal and global cerebral ischemia, traumatic brain injury, excitotoxicity, epilepsy, Alzheimer’s disease, and Parkinson’s disease. Much of what we have learned about BDE2 in neurological disorders has come from use of aromatase inhibitors and global aromatase knockout mice. Recently, our group developed astrocyte- and neuron-specific aromatase knockout mice, which have helped to clarify the precise functions of astrocyte-derived 17β-estradiol (ADE2) and neuron-derived 17β-estradiol (NDE2) in the brain. The available evidence to date suggests a primarily beneficial role of BDE2 in facilitating neuroprotection, synaptic and cognitive preservation, regulation of reactive astrocyte and microglia activation, and anti-inflammatory effects. Most of these beneficial effects appear to be due to ADE2, which is induced in most neurological disorders, but there is also recent evidence that NDE2 exerts similar beneficial effects. Furthermore, in certain situations, BDE2 may also have deleterious effects, as recent evidence suggests its overproduction in epilepsy contributes to seizure induction. In this review, we examine the current state of this quickly developing topic, as well as possible future studies that may be required to provide continuing growth in the field.

Original languageEnglish (US)
Article number1698
JournalBiology
Volume11
Issue number12
DOIs
StatePublished - Dec 2022

Keywords

  • Alzheimer’s disease
  • aromatase
  • cerebral ischemia
  • epilepsy
  • estradiol
  • neurodegeneration
  • neuroestrogen
  • neurosteroid
  • Parkinson’s disease
  • traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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