Genes preferentially induced by depolarization after concussive brain injury: effects of age and injury severity.
Fluid percussion (FP) brain injury leads to immediate indiscriminate depolarization and massive potassium efflux from neurons. Using Northern blotting, we examined the post-FP expression of primary response/immediate early genes previously described as induced by depolarization in brain. RNA from ipsilateral and contralateral hippocampus was harvested from immature and adult rats 1 h following mild, moderate, or severe lateral fluid percussion injury and compared against age-matched sham animals. C-fos gene expression was used as a positive control and showed marked induction in both pups (6-25-fold with increasing severity) and adults (9.7-17.1-fold). Kinase-induced-by-depolarization-1 (KID-1) and salt-inducible kinase (SIK) gene expression was increased in adult (KID-1 1.5-1.6-fold; SIK 1.3-3.9-fold) but not developing rats. NGFI-b RNA was elevated after injury in both ages (pups 1.8-6.1-fold; adults 3.5-5-fold), in a pattern similar to that seen for c-fos. Secretogranin I (sec I) demonstrated no significant changes. Synaptotagmin IV (syt IV) was induced only following severe injury in the immature rats (1.4-fold). Our results reveal specific severity- and age-dependent patterns of hippocampal immediate early gene expression for these depolarization-induced genes following traumatic brain injury. Differential expression of these genes may be an important determinant of the distinct molecular responses of the brain to varying severities of trauma experienced at different ages.
Giza
Christopher C
CC
Division of Neurosurgery, UCLA School of Medicine, 90095, USA. cgiza@mednet.ucla.edu
Prins
Mayumi L
ML
Hovda
David A
DA
Herschman
Harvey R
HR
Feldman
Jonathan D
JD
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002135:Calcium-Binding Proteins; D002864:Chromogranins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D017781:Genes, Immediate-Early / Q000502:physiology*; D016762:Genes, fos / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D050857:Synaptotagmins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002135:Calcium-Binding Proteins; D002864:Chromogranins; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; C494294:Syt4 protein, rat; D014157:Transcription Factors; D050857:Synaptotagmins; C113398:Pim3 protein, rat; D017346:Protein Serine-Threonine Kinases; C120299:Sik1 protein, rat