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Reproductive hormones regulate the selective permeability of the blood-brain barrier.
Biochim Biophys Acta 2008; 1782(6):401-7BB

Abstract

Reproductive hormones have been demonstrated to modulate both gap and tight junction protein expression in the ovary and other reproductive tissues, however the effects of changes in reproductive hormones on the selective permeability of the blood-brain barrier (BBB) remain unclear. Age-related declines in BBB integrity correlate with the loss of serum sex steroids and increase in gonadotropins with menopause/andropause. To examine the effect of reproductive senescence on BBB permeability and gap and tight junction protein expression/localization, female mice at 3 months of age were either sham operated (normal serum E2 and gonadotropins), ovariectomized (low serum E2 and high serum gonadotropins) or ovariectomized and treated with the GnRH agonist leuprolide acetate (low serum E2 and gonadotropins). Ovariectomy induced a 2.2-fold increase in Evan's blue dye extravasation into the brain. The expression and localization of the cytoplasmic membrane-associated tight junction protein zona occludens 1 (ZO-1) in microvessels was not altered among groups indicating that the increased paracellular permeability was not due to changes in this tight junction protein. However, ovariectomy induced a redistribution of the gap junction protein connexin-43 (Cx43) such that immunoreactivity relocalized from along the extracellular microvascular endothelium to become associated with endothelial cells. An increase in Cx43 expression in the mouse brain following ovariectomy was suppressed in ovariectomized animals treated with leuprolide acetate, indicating that serum gonadotropins rather than sex steroids were modulating Cx43 expression. These results suggest that elevated serum gonadotropins following reproductive senescence may be one possible cause of the loss of selective permeability of the BBB at this time. Furthermore, these findings implicate Cx43 in mediating changes in BBB permeability, and serum gonadotropins in the cerebropathophysiology of age-related neurodegenerative diseases such as stroke and Alzheimer's disease.

Authors+Show Affiliations

Department of Medicine, University of Wisconsin-Madison and Geriatric Research, Education and Clinical Center, Veterans Administration Hospital, 2500 Overlook Terrace, Madison, WI 53705 USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18381207

Citation

Wilson, Andrea C., et al. "Reproductive Hormones Regulate the Selective Permeability of the Blood-brain Barrier." Biochimica Et Biophysica Acta, vol. 1782, no. 6, 2008, pp. 401-7.
Wilson AC, Clemente L, Liu T, et al. Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochim Biophys Acta. 2008;1782(6):401-7.
Wilson, A. C., Clemente, L., Liu, T., Bowen, R. L., Meethal, S. V., & Atwood, C. S. (2008). Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochimica Et Biophysica Acta, 1782(6), pp. 401-7. doi:10.1016/j.bbadis.2008.02.011.
Wilson AC, et al. Reproductive Hormones Regulate the Selective Permeability of the Blood-brain Barrier. Biochim Biophys Acta. 2008;1782(6):401-7. PubMed PMID: 18381207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reproductive hormones regulate the selective permeability of the blood-brain barrier. AU - Wilson,Andrea C, AU - Clemente,Luca, AU - Liu,Tianbing, AU - Bowen,Richard L, AU - Meethal,Sivan Vadakkadath, AU - Atwood,Craig S, Y1 - 2008/03/14/ PY - 2007/10/23/received PY - 2008/02/21/revised PY - 2008/02/25/accepted PY - 2008/4/3/pubmed PY - 2008/9/23/medline PY - 2008/4/3/entrez SP - 401 EP - 7 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1782 IS - 6 N2 - Reproductive hormones have been demonstrated to modulate both gap and tight junction protein expression in the ovary and other reproductive tissues, however the effects of changes in reproductive hormones on the selective permeability of the blood-brain barrier (BBB) remain unclear. Age-related declines in BBB integrity correlate with the loss of serum sex steroids and increase in gonadotropins with menopause/andropause. To examine the effect of reproductive senescence on BBB permeability and gap and tight junction protein expression/localization, female mice at 3 months of age were either sham operated (normal serum E2 and gonadotropins), ovariectomized (low serum E2 and high serum gonadotropins) or ovariectomized and treated with the GnRH agonist leuprolide acetate (low serum E2 and gonadotropins). Ovariectomy induced a 2.2-fold increase in Evan's blue dye extravasation into the brain. The expression and localization of the cytoplasmic membrane-associated tight junction protein zona occludens 1 (ZO-1) in microvessels was not altered among groups indicating that the increased paracellular permeability was not due to changes in this tight junction protein. However, ovariectomy induced a redistribution of the gap junction protein connexin-43 (Cx43) such that immunoreactivity relocalized from along the extracellular microvascular endothelium to become associated with endothelial cells. An increase in Cx43 expression in the mouse brain following ovariectomy was suppressed in ovariectomized animals treated with leuprolide acetate, indicating that serum gonadotropins rather than sex steroids were modulating Cx43 expression. These results suggest that elevated serum gonadotropins following reproductive senescence may be one possible cause of the loss of selective permeability of the BBB at this time. Furthermore, these findings implicate Cx43 in mediating changes in BBB permeability, and serum gonadotropins in the cerebropathophysiology of age-related neurodegenerative diseases such as stroke and Alzheimer's disease. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/18381207/Reproductive_hormones_regulate_the_selective_permeability_of_the_blood_brain_barrier_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4439(08)00060-4 DB - PRIME DP - Unbound Medicine ER -