Neuron-specific mRNA complexity responses during hippocampal apoptosis after traumatic brain injury.
In an effort to understand the complexity of genomic responses within selectively vulnerable regions after experimental brain injury, we examined whether single apoptotic neurons from both the CA3 and dentate differed from those in an uninjured brain. The mRNA from individual active caspase 3(+)/terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling [TUNEL(-)] and active caspase 3(+)/TUNEL(+) pyramidal and granule neurons in brain-injured mice were amplified and compared with those from nonlabeled neurons in uninjured brains. Gene analysis revealed that overall expression of mRNAs increased with activation of caspase 3 and decreased to below uninjured levels with TUNEL reactivity. Cell type specificity of the apoptotic response was observed with both regionally distinct expression of mRNAs and differences in those mRNAs that were maximally regulated. Immunohistochemical analysis for two of the most highly differentially expressed genes (prion and Sos2) demonstrated a correlation between the observed differential gene expression after traumatic brain injury and corresponding protein translation.
Marciano
Paolo G
PG
Departments of Neuroscience, Center for Bioinformatics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Brettschneider
Julia
J
Manduchi
Elisabetta
E
Davis
Jason E
JE
Eastman
Scott
S
Raghupathi
Ramesh
R
Saatman
Kathryn E
KE
Speed
Terence P
TP
Stoeckert
Christian J
CJ
Eberwine
James H
JH
McIntosh
Tracy K
TK
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D018621:PrPC Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020664:Son of Sevenless Proteins / Q000096:biosynthesis
D018621:PrPC Proteins; D012333:RNA, Messenger; D020664:Son of Sevenless Proteins; C116864:Sos2 protein, mouse