Neuron-specific mRNA complexity responses during hippocampal apoptosis after traumatic brain injury

被引:33
作者
Marciano, PG
Brettschneider, J
Manduchi, E
Davis, JE
Eastman, S
Raghupathi, R
Saatman, KE
Speed, TP
Stoeckert, CJ
Eberwine, JH
McIntosh, TK
机构
[1] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA
[3] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA
[4] Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA
[5] Vet Adm Med Ctr, Philadelphia, PA 19104 USA
[6] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA
[7] Incyte Genom, Palo Alto, CA 94304 USA
关键词
apoptosis; traumatic brain injury; hippocampus; CA3; dentate; single-cell amplification; microarray; cell death; differential expression; real-time quantitative PCR;
D O I
10.1523/JNEUROSCI.5051-03.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:2866 / 2876
页数:11
相关论文
共 61 条
[51]   A MODEL OF PARASAGITTAL CONTROLLED CORTICAL IMPACT IN THE MOUSE - COGNITIVE AND HISTOPATHOLOGIC EFFECTS [J].
SMITH, DH ;
SOARES, HD ;
PIERCE, JS ;
PERLMAN, KG ;
SAATMAN, KE ;
MEANEY, DF ;
DIXON, CE ;
MCINTOSH, TK .
JOURNAL OF NEUROTRAUMA, 1995, 12 (02) :169-178
[52]  
Smith PM, 2002, J SPORT SCI, V20, P27
[53]   Resistance of actin to cleavage during apoptosis [J].
Song, QZ ;
Wei, T ;
LeesMiller, S ;
Alnemri, E ;
Watters, D ;
Lavin, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (01) :157-162
[54]   HEAD-INJURY - ASSOCIATED DEATHS IN THE UNITED-STATES FROM 1979 TO 1986 [J].
SOSIN, DM ;
SACKS, JJ ;
SMITH, SM .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1989, 262 (16) :2251-2255
[55]   Increased sensitivity to seizures in mice lacking cellular prion protein [J].
Walz, R ;
Amaral, OB ;
Rockenbach, IC ;
Roesler, R ;
Izquierdo, I ;
Cavalheiro, EA ;
Martins, VR ;
Brentani, RR .
EPILEPSIA, 1999, 40 (12) :1679-1682
[56]   In situ DNA fragmentation occurs in white matter up to 12 months after head injury in man [J].
Williams, S ;
Raghupathi, R ;
MacKinnon, MA ;
McIntosh, TK ;
Saatman, KE ;
Graham, DI .
ACTA NEUROPATHOLOGICA, 2001, 102 (06) :581-590
[57]  
Yakovlev AG, 1997, J NEUROSCI, V17, P7415
[58]   Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation [J].
Yang, YH ;
Dudoit, S ;
Luu, P ;
Lin, DM ;
Peng, V ;
Ngai, J ;
Speed, TP .
NUCLEIC ACIDS RESEARCH, 2002, 30 (04) :e15
[59]  
YANG YH, 2002, J COMPUT GRAPH STAT, V11, P1
[60]  
YANG YH, 2002, MICROARRAYS OPTICAL, P141