Estrogen facilitates neurite extension via apolipoprotein E in cultured adult mouse cortical neurons

Britto P. Nathan, Anna Bell, Fei Shen, Mary McAsey, Robert G. Struble

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Literature review suggests a close relationship between estrogen and apolipoprotein E (ApoE) in the central nervous system. Epidemiology studies show that estrogen replacement therapy (ERT) decreases the morbidity from several chronic neurological diseases. Alleles of ApoE modify the risk for and progression of the same diseases. ApoE levels in the rodent brain vary during the estrous cycle and increase after 17β-estradiol administration. Both estradiol and ApoE3, the most common isoform of human ApoE, increase the extent of neurite outgrowth in culture. Combined, these observations suggest a common mechanism whereby estrogen may increase ApoE levels to facilitate neurite growth. We tested this hypothesis by characterizing the effects of estradiol and ApoE isoforms on neurite outgrowth in cultured adult mouse cortical neurons. Estradiol increased ApoE levels and neurite outgrowth. ApoE2 increased neurite length more so than ApoE3 in the presence of estradiol. Estradiol had no effect on neurite outgrowth from mice lacking the ApoE gene or when only ApoE4, the isoform of ApoE that is associated with increased risk of neurological disease, was exogenously supplied. Cultures from mice transgenic for human ApoE3 or ApoE4 showed the same isoform-specific effect. Neuronal internalization of recombinant human ApoE3 was greater than ApoE4, and ApoE3 was more effective than ApoE4 in facilitating neuronal uptake of a fatty acid. We conclude that estradiol facilitates neurite growth through an ApoE-dependent mechanism. The effects of ERT on chronic neurological diseases may vary with ApoE genotype. The clinical use of ERT may require ApoE genotyping for optimal efficacy.

Original languageEnglish (US)
Pages (from-to)3065-3073
Number of pages9
JournalEndocrinology
Volume145
Issue number7
DOIs
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Apolipoproteins E
Neurites
Estrogens
Neurons
Apolipoprotein E3
Estradiol
Apolipoprotein E4
Estrogen Replacement Therapy
Protein Isoforms
Chronic Disease
Apolipoprotein E2
Estrous Cycle
Growth
Transgenic Mice
Disease Progression
Rodentia
Epidemiology
Fatty Acids
Central Nervous System
Alleles

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Estrogen facilitates neurite extension via apolipoprotein E in cultured adult mouse cortical neurons. / Nathan, Britto P.; Bell, Anna; Shen, Fei; McAsey, Mary; Struble, Robert G.

In: Endocrinology, Vol. 145, No. 7, 07.2004, p. 3065-3073.

Research output: Contribution to journalArticle

Nathan, Britto P. ; Bell, Anna ; Shen, Fei ; McAsey, Mary ; Struble, Robert G. / Estrogen facilitates neurite extension via apolipoprotein E in cultured adult mouse cortical neurons. In: Endocrinology. 2004 ; Vol. 145, No. 7. pp. 3065-3073.
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