Myocardial ischemia/reperfusion impairs neurogenesis and hippocampal-dependent learning and memory.
The incidence of cognitive impairment in cardiovascular disease (CVD) patients has increased, adversely impacting quality of life and imposing a significant economic burden. Brain imaging of CVD patients has detected changes in the hippocampus, a brain region critical for normal learning and memory. However, it is not clear whether adverse cardiac events or other associated co-morbidities impair cognition. Here, using a murine model of acute myocardial ischemia/reperfusion (I/R), where the coronary artery was occluded for 30min followed by reperfusion, we tested the hypothesis that acute myocardial infarction triggers impairment in cognitive function. Two months following cardiac I/R, behavioral assessments specific for hippocampal cognitive function were performed. Mice subjected to cardiac I/R performed worse in the fear-conditioning paradigm as well as the object location memory behavioral test compared to sham-operated mice. Reactive gliosis was apparent in the hippocampal subregions CA1, CA3, and dentate gyrus 72h post-cardiac I/R as compared with sham, which was sustained two months post-cardiac I/R. Consistent with the inflammatory response, the abundance of doublecortin positive newborn neurons was decreased in the dentate gyrus 72h and 2months post-cardiac I/R as compared with sham. Therefore, we conclude that following acute myocardial infarction, rapid inflammatory responses negatively affect neurogenesis, which may underlie long-term changes in learning and memory.
Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Physical Medicine Rehabilitation, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Kirsten S
KS
Evonuk
Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Sumanth D
SD
Prabhu
Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Martin E
ME
Young
Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Physical Medicine Rehabilitation, University of Alabama at Birmingham, Birmingham, AL 35294, United States; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, United States. Electronic address: desilvat@uab.edu.
Tara M
TM
DeSilva
D000818:Animals; D003071:Cognition / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000523:psychology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology
Cognition; Myocardial infarction; Neuroinflammation; Reactive gliosis