title: Physiologic Reelin does not play a strong role in protection against acute stroke.
abstract: Stroke and Alzheimer's disease, two diseases that disproportionately affect the aging population, share a subset of pathological findings and risk factors. The primary genetic risk factor after age for late-onset Alzheimer's disease, ApoE4, has also been shown to increase stroke risk and the incidence of post-stroke dementia. One mechanism by which ApoE4 contributes to disease is by inducing in neurons a resistance to Reelin, a neuromodulator that enhances synaptic function. Previous studies in Reelin knockout mice suggest a role for Reelin in protection against stroke; however, these studies were limited by the developmental requirement for Reelin in neuronal migration. To address the question of the effect of Reelin loss on stroke susceptibility in an architecturally normal brain, we utilized a novel mouse with induced genetic reduction of Reelin. We found that after transient middle cerebral artery occlusion, mice with complete adult loss of Reelin exhibited a similar level of functional deficit and extent of infarct as control mice. Together, these results suggest that physiological Reelin does not play a strong role in protection against stroke pathology.
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA Center for Translational Neurodegeneration Research, Dallas, TX, USA courtney.lane@utsouthwestern.edu.
authors.forename: Courtney
authors.initials: C
authors.lastname: Lane-Donovan
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Charisma
authors.initials: C
authors.lastname: Desai
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA Center for Translational Neurodegeneration Research, Dallas, TX, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Pohlkamp
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Plautz
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA Center for Translational Neurodegeneration Research, Dallas, TX, USA Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA Center for Neuroscience, Department of Neuroanatomy, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Herz
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Stowe
mesh_terms: D000818:Animals; D053327:Apolipoprotein E4 / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D045442:Rotarod Performance Test; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D020521:Stroke / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D053327:Apolipoprotein E4; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: ApoE4; Reelin; Reelin conditional knockout; stroke; transient middle cerebral artery occlusion