Recently, several studies have reported on the hormonal regulation, particularly estrogen, on neurodegenerative diseases. Although the precise role of estrogen in neurodegenerative diseases remains unclear, evidence has emerged regarding estrogen’s neuroprotective effect in Alzheimer’s Disease(1). Though animal models of neurodegenerative diseases have been studied extensively, many studies still use primary brain cell cultures. Most harvest fetal rodent brains at embryological day18 (E18) to evaluate hormonal effects on neurodegeneration as well as hormone receptor expression(1-3). The justification for using E18 culturesis that neuronal circuits are relatively plastic and uniform rendering it an excellent in vitro model. Additionally, prior to sexual differentiation, the default brain is "female". Therefore, differentiating female and male pups at E18 has traditionally been ignored. Such studies fail to acknowledge that sexual differences can be determined as early as E11 of rodent gestation(3-5). In other words, hormone receptor expression throughout the brain may be different between sexes. Furthermore, density of hormone receptors within a particular region may also be different between sexes. To circumvent the differences of hormone receptor expression between the sexes, cell cultures should be taken before the second trimester to ensure that all embryo brains are female. Based on emerging work in hormonal regulation, experimental results may be influenced by sex-based receptor expression on E18. Understanding the hormone expression throughout the brain in both sexes should be noted in order to clearly define the mechanism of action of a hormone and its relation to a particular disease.
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