Article

Molecular and Cellular Biochemistry

, Volume 369, Issue 1, pp 267-286

Gene expression changes of interconnected spared cortical neurons 7 days after ischemic infarct of the primary motor cortex in the rat

  • Edward T. R. UrbanIIIAffiliated withDepartment of Molecular & Integrative Physiology, Kansas University Medical CenterLandon Center on Aging, Kansas University Medical Center
  • , Scott D. BuryAffiliated withLandon Center on Aging, Kansas University Medical Center
  • , H. Scott BarbayAffiliated withLandon Center on Aging, Kansas University Medical Center
  • , David J. GuggenmosAffiliated withDepartment of Molecular & Integrative Physiology, Kansas University Medical CenterLandon Center on Aging, Kansas University Medical Center
  • , Yafeng DongAffiliated withDepartment of Obstetrics and Gynecology, Kansas University Medical Center
  • , Randolph J. NudoAffiliated withDepartment of Molecular & Integrative Physiology, Kansas University Medical CenterLandon Center on Aging, Kansas University Medical CenterIntellectual & Developmental Disabilities Research Center, Kansas University Medical Center Email author 

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Abstract

After cortical injury resulting from stroke, some recovery can occur and may involve spared areas of the cerebral cortex reorganizing to assume functions previously controlled by the damaged cortical areas. No studies have specifically assessed gene expression changes in remote neurons with axonal processes that terminate in the infarcted tissue, i.e., the subset of neurons most likely to be involved in regenerative processes. By physiologically identifying the primary motor area controlling forelimb function in adult rats (caudal forelimb area = CFA), and injecting a retrograde tract-tracer, we labeled neurons within the non-primary motor cortex (rostral forelimb area = RFA) that project to CFA. Then, 7 days after a CFA infarct (n = 6), we used laser capture microdissection techniques to harvest labeled neurons in RFA. Healthy, uninjured rats served as controls (n = 6). Biological interactions and functions of gene profiling were investigated by Affymetrix Microarray, and Ingenuity Pathway Analysis. A total of 143 up- and 128 down-regulated genes showed significant changes (fold change ≥1.3 and p < 0.05). The canonical pathway, “Axonal Guidance Signaling,” was overrepresented (p value = 0.002). Significantly overrepresented functions included: branching of neurites, organization of cytoskeleton, dendritic growth and branching, organization of cytoplasm, guidance of neurites, development of cellular protrusions, density of dendritic spines, and shape change (p = 0.000151–0.0487). As previous studies have shown that spared motor areas are important in recovery following injury to the primary motor area, the results suggest that these gene expression changes in remote, interconnected neurons may underlie reorganization and recovery mechanisms.

Keywords

Stroke Ischemic infarct Motor cortex Plasticity Gene expression