Interleukin 6 reduces allopregnanolone synthesis in the brain and contributes to age-related cognitive decline in mice.

Journal of Lipid Research
Eileen E ParksWilliam E Sonntag

Abstract

Cognitive decline with age is a harmful process that can reduce quality of life. Multiple factors have been established to contribute to cognitive decline, but the overall etiology remains unknown. Here, we hypothesized that cognitive dysfunction is mediated, in part, by increased levels of inflammatory cytokines that alter allopregnanolone (AlloP) levels, an important neurosteroid in the brain. We assessed the levels and regulation of AlloP and the effects of AlloP supplementation on cognitive function in 4-month-old and 24-month-old male C57BL/6 mice. With age, the expression of enzymes involved in the AlloP synthetic pathway was decreased and corticosterone (CORT) synthesis increased. Supplementation of AlloP improved cognitive function. Interestingly, interleukin 6 (IL-6) infusion in young animals significantly reduced the production of AlloP compared with controls. It is notable that inhibition of IL-6 with its natural inhibitor, soluble membrane glycoprotein 130, significantly improved spatial memory in aged mice. These findings were supported by in vitro experiments in primary murine astrocyte cultures, indicating that IL-6 decreases production of AlloP and increases CORT levels. Our results indicate that age-related inc...Continue Reading

References

Jun 23, 1999·Journal of Neuroimmunology·S M Ye, R W Johnson
Feb 9, 2000·Frontiers in Neuroendocrinology·N A Compagnone, S H Mellon
Jul 19, 2006·Learning & Memory·Laetitia FelliniFabio Morellini
Aug 18, 2006·Journal of Alzheimer's Disease : JAD·Eliezer MasliahLawrence Hansen
Dec 2, 2006·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Geoffrey G MurphyAlcino J Silva
Oct 24, 2007·General and Comparative Endocrinology·A E M NewmanK K Soma
Apr 25, 2009·Immunology and Allergy Clinics of North America·Jonathan P Godbout, Rodney W Johnson
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jun Ming WangRoberta Diaz Brinton
May 19, 2010·Progress in Brain Research·Georges Pelletier
Jan 18, 2011·Prostaglandins & Other Lipid Mediators·Krishna Rao Maddipati, Sen-Lin Zhou
Feb 14, 2012·Biochimica Et Biophysica Acta·Hongen WeiXiaohong Li
Jan 1, 2011·Frontiers in Endocrinology·Alessandro Faroni, Valerio Magnaghi
Nov 9, 2012·International Journal of Biological Sciences·Stefan Rose-John
Jun 12, 2014·Frontiers in Cellular Neuroscience·Farshid NoorbakhshChristopher Power
Jul 26, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Krishna Rao MaddipatiKenneth V Honn
Aug 16, 2014·Frontiers in Cellular Neuroscience·Ronald W IrwinRoberta Diaz Brinton
Oct 5, 2014·Experimental Gerontology·Shankar J ChintaJulie K Andersen
Mar 27, 2016·Biochimica Et Biophysica Acta·Michelle RothaugStefan Rose-John
Feb 6, 2017·Neuroscience and Biobehavioral Reviews·Svetlana Di BenedettoGraham Pawelec
Mar 17, 2017·Cell Death & Disease·Lin-Hao YouYan-Zhong Chang
Apr 26, 2017·The EMBO Journal·Simonetta Camandola, Mark P Mattson
Oct 17, 2017·Trends in Endocrinology and Metabolism : TEM·Walter L Miller
Apr 17, 2019·International Journal of Molecular Sciences·Michelle A Erickson, William A Banks

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Citations

Nov 5, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Gabryella S P SantosAlexander Birbrair

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Methods Mentioned

BETA
protein assay

Software Mentioned

JMP
PhenoTyper
Systat
MultiQuant
SAS
Analyst
GraphPad Prism
Ethovision

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