Apolipoprotein E-genotype dependent hippocampal and cortical responses to traumatic brain injury.
The different alleles of the apolipoprotein E gene (APOE-gene, ApoE-protein) have been reported to influence recovery after traumatic brain injury (TBI) in both human patients and animal models, with the e4 allele typically conferring poorer prognosis for recovery. How the E4 allele, and consequently the ApoE4 isoform, affects recovery is unknown, but proposed mechanisms include neurogenesis, inflammatory response and amyloid processing or metabolism. Using the controlled cortical impact (CCI) model of brain injury and microarray technology we have characterized the genomic response to injury in the brains of APOE2, APOE3 and APOE4 transgenic mice and identified quantitatively and qualitatively significantly different profiles of gene expression in both the hippocampus and the cortex of the APOE3 mice compared to APOE4. The observed gene regulation predicts functional consequences including effects on inflammatory processes, cell growth and proliferation, and cellular signaling, and may suggest that the poor recovery post-TBI in APOE4 animals and human patients is less likely to result from a specific activation of neurodegenerative mechanisms than a loss of reparative capability.
Crawford
F
F
Roskamp Institute, Sarasota, FL 34243, USA. fcrawford@rfdn.org
Wood
M
M
Ferguson
S
S
Mathura
V
V
Gupta
P
P
Humphrey
J
J
Mouzon
B
B
Laporte
V
V
Margenthaler
E
E
O'Steen
B
B
Hayes
R
R
Roses
A
A
Mullan
M
M
D000818:Animals; D053329:Apolipoprotein E2 / Q000235:genetics*; D053318:Apolipoprotein E3 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001930:Brain Injuries / Q000235:genetics* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000503:physiopathology*; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005838:Genotype; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012984:Software
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D020033:Protein Isoforms