APOE4 genetic polymorphism results in impaired recovery in a repeated mild traumatic brain injury model and treatment with Bryostatin-1 improves outcomes.

Scientific Reports
Anna O GiarratanaJanet Alder

Abstract

After traumatic brain injury (TBI), some people have worse recovery than others. Single nucleotide polymorphisms (SNPs) in Apolipoprotein E (APOE) are known to increase risk for developing Alzheimer's disease, however there is controversy from human and rodent studies as to whether ApoE4 is a risk factor for worse outcomes after brain trauma. To resolve these conflicting studies we have explored the effect of the human APOE4 gene in a reproducible mouse model that mimics common human injuries. We have investigated cellular and behavioral outcomes in genetically engineered human APOE targeted replacement (TR) mice following repeated mild TBI (rmTBI) using a lateral fluid percussion injury model. Relative to injured APOE3 TR mice, injured APOE4 TR mice had more inflammation, neurodegeneration, apoptosis, p-tau, and activated microglia and less total brain-derived neurotrophic factor (BDNF) in the cortex and/or hippocampus at 1 and/or 21 days post-injury. We utilized a novel personalized approach to treating APOE4 susceptible mice by administering Bryostatin-1, which improved cellular as well as motor and cognitive behavior outcomes at 1 DPI in the APOE4 injured mice. This study demonstrates that APOE4 is a risk factor for poor ou...Continue Reading

References

Sep 1, 1991·Brain Research. Molecular Brain Research·J PoirierC E Finch
Dec 1, 1996·Neuropathology and Applied Neurobiology·J A Nicoll
Aug 26, 1998·Experimental Neurology·G K ZupancH Schwarz
Jun 8, 1999·The Journal of Clinical Investigation·C KnouffN Maeda
Nov 10, 2001·Annual Review of Genomics and Human Genetics·R W Mahley, S C Rall
Mar 26, 2002·The Journal of Biological Chemistry·Zhong-Sheng JiRobert W Mahley
Mar 11, 2003·Critical Care Medicine·Eduardo MiñambresFrancisco Leyva-Cobián
Aug 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Faith M HarrisYadong Huang
Sep 26, 2003·The Journal of Biological Chemistry·John R LynchDaniel T Laskowitz
Jun 8, 2004·Journal of Molecular Neuroscience : MN·Ling GuoLinda J Van Eldik
Aug 18, 2004·Journal of Neurosurgery·Narendra NathooRunjan Chetty
Jan 25, 2005·Journal of Neurotrauma·Hilaire J ThompsonTracy K McIntosh
Nov 22, 2005·The Journal of Biological Chemistry·Zhong-Sheng JiRobert W Mahley
May 12, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qin XuYadong Huang
Apr 5, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Daniela BermpohlMichael J Whalen
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Dec 25, 2007·Neurobiology of Aging·Michael P VitekCarol A Colton
Apr 1, 2008·Journal of Neurotrauma·Weidong ZhouKeith A Crutcher
Jul 11, 2008·Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine·Vicki L KristmanPaul Comper
Jul 17, 2009·The New England Journal of Medicine·Richard J CaselliEric M Reiman
Jul 1, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Rebekah C MannixMichael J Whalen
Aug 25, 2010·American Journal of Physical Anthropology·Dan T A EisenbergM Geoffrey Hayes
Nov 17, 2010·Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine·Ryan T TierneyEvgeny Krynetskiy
Jan 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jarin HongpaisanDaniel L Alkon
May 4, 2011·Brain Injury : [BI]·Rahida Mohd ShadliFaridah Abdul Rashid
Aug 31, 2011·Journal of Visualized Experiments : JoVE·Janet AlderSmita Thakker-Varia
Feb 1, 2012·Frontiers in Molecular Neuroscience·Clifton L DalgardWilliam D Watson
Jun 30, 2012·The British Journal of Psychiatry : the Journal of Mental Science·Jennifer J VasterlingMolly Franz
Dec 12, 2012·Neuron·Robert W Mahley, Yadong Huang
Dec 18, 2012·British Journal of Sports Medicine·Kimberly G HarmonWilliam O Roberts
Jan 19, 2013·Nature Reviews. Neuroscience·Ye XiongMichael Chopp
Apr 16, 2013·Journal of Neuropathology and Experimental Neurology·Rachel E BennettDavid L Brody
Jul 13, 2013·Frontiers in Neurology·Wendy NobleSimon Lovestone
Aug 8, 2013·Annals of Neurology·Rebekah MannixMichael Whalen
Sep 17, 2013·Pharmaceutical Biology·Peter KollárJiří Pazourek
Nov 1, 2013·Stroke; a Journal of Cerebral Circulation·Zhenjun TanJason D Huber

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Citations

Aug 12, 2021·Experimental Neurobiology·Sung Eun LeeSun Ah Park

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Methods Mentioned

BETA
Protein Assay
enzyme-linked immunosorbent assay
ELISA
nuclear translocation

Software Mentioned

VivoQuant
EthoVision
Quantity One
Multiplex

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