Zinc supplementation normalizes gene expression and enhances neurogenesis in a rat model of traumatic brain injury
Abstract
New interventions are needed to improve resilience to traumatic brain injury (TBI). To examine the role of zinc, rats were fed a zinc adequate (30 ppm) or supplemented (180 ppm) diet for 4 wks followed by a frontal cortex TBI using controlled cortical impact. Chronic zinc supplementation significantly improved spatial learning and memory, and reduced anxiety and depression‐like behaviors. Mechanistically, we hypothesized that zinc supplementation would prevent injury‐induced changes in gene expression and enhance hippocampal stem cell proliferation and survival. Hippocampal RNA was extracted 48 h after TBI to analyze mRNA abundance via the NimbleGen platform microarray. TBI altered the expression of over 170 mRNAs, approximately 70 of which were normalized in rats supplemented with zinc (p<0.01). We identified genes involved in cell proliferation, apoptosis, survival, repair, and differentiation. Rats were also injected with the thymidine analogue EdU to label proliferating cells in the hippocampus. TBI doubled the number of proliferating cells in the dentate gyrus granular cell layer 24 h post‐injury (p<0.05), and supplemental zinc increased this number by an additional 2 fold (p<0.05). Ongoing work is characterizing the long‐term fate of these cells. These data show that zinc can be a novel and effective strategy for preventing adverse cellular, molecular, and behavioral outcomes associated with TBI.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2013
- Source ID
- 10.1096/fasebj.27.1_supplement.234.1
Entities
People
- Cathy W. Levenson
- Elise C. Cope
Organizations
- Florida State University
- United States Army Medical Research and Development Command