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.
Original language | English |
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Pages (from-to) | 1295-1303 |
Number of pages | 9 |
Journal | Journal of Cerebral Blood Flow and Metabolism |
Volume | 36 |
Issue number | 7 |
DOIs | |
State | Published - Jul 1 2016 |
Bibliographical note
Publisher Copyright:© The Author(s) 2016.
Funding
This work was supported by NIH grants F30AG047799 (to CLD), R37HL63762 (to JH), R01NS093382 (to JH), and R01NS088555 (to AMS), the American Health Assistance Foundation, the Consortium for Frontotemporal Dementia Research, the Bright Focus Foundation, the Lupe Murchison Foundation, the Ted Nash Long Life Foundation, the Deutsche Forschungsgemeinschaft (DFG) (grant numbers SFB 780/TP5 to JH), the American Heart Association (14SDG18410020 to AMS), and the Haggerty Center for Brain Injury and Repair (UTSW, to AMS).
Funders | Funder number |
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Bright Focus Foundation | |
Consortium for Frontotemporal Dementia Research | |
Ted Nash Long Life Foundation | |
National Institutes of Health (NIH) | R01NS088555, R37HL63762, R01NS093382 |
National Institute on Aging | F30AG047799 |
American Health Assistance Foundation | |
American Heart Association | 14SDG18410020 |
Lupe Murchison Foundation | |
Deutsche Forschungsgemeinschaft | SFB 780/TP5 |
Keywords
- ApoE4
- Reelin
- Reelin conditional knockout
- stroke
- transient middle cerebral artery occlusion
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine