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Front Aging Neurosci. 2017 Dec 8;9:383. doi: 10.3389/fnagi.2017.00383. eCollection 2017.

Hippocampal Transcriptomic Profiles: Subfield Vulnerability to Age and Cognitive Impairment.

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Departments of Neuroscience and Genetics and Genomics Program, Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, United States.
Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL, United States.
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, United States.
Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, United States.
Evelyn F. McKnight Brain Institute, University of Alabama, Birmingham, AL, United States.
Department of Pharmacology, Vanderbilt University, Nashville, TN, United States.
Departments of Psychology, Neurology and Neuroscience, University of Arizona, Tucson, AZ, United States.


The current study employed next-generation RNA sequencing to examine gene expression differences related to brain aging, cognitive decline, and hippocampal subfields. Young and aged rats were trained on a spatial episodic memory task. Hippocampal regions CA1, CA3, and the dentate gyrus were isolated. Poly-A mRNA was examined using two different sequencing platforms, Illumina, and Ion Proton. The Illumina platform was used to generate seed lists of genes that were statistically differentially expressed across regions, ages, or in association with cognitive function. The gene lists were then retested using the data from the Ion Proton platform. The results indicate hippocampal subfield differences in gene expression and point to regional differences in vulnerability to aging. Aging was associated with increased expression of immune response-related genes, particularly in the dentate gyrus. For the memory task, impaired performance of aged animals was linked to the regulation of Ca2+ and synaptic function in region CA1. Finally, we provide a transcriptomic characterization of the three subfields regardless of age or cognitive status, highlighting and confirming a correspondence between cytoarchitectural boundaries and molecular profiling.


Illumina HiSeq; Ion proton; aging; cognitive function; gene expression; hippocampus; transcription

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