The synthetic NCAM-derived peptide, FGL, modulates the transcriptional response to traumatic brain injury.
Cerebral responses to traumatic brain injury (TBI) include up- and downregulation of a vast number of proteins involved in endogenous inflammatory responses and defense mechanisms developing postinjury. The present study analyzed the global gene expression profile in response to cryo-induced TBI by means of microarray analysis. Adolescent rats were subjected to TBI and treated with either placebo or a neural cell adhesion molecule (NCAM)-derived fibroblast growth factor receptor (FGFR) agonist, FGL peptide, which has been demonstrated to have neuroprotective effects. mRNA levels were measured at various time-points postlesion (6 h, 1 day and 4 days). The effects of injury, treatment, and injury-treatment interaction were observed. TBI alone rendered a large number of genes affected. Analysis of lesion and treatment interactions resulted in a clear effect of the interaction between injury and FGL-treatment compared to injury and placebo-treatment. Genes affected by TBI alone included inflammation markers, protein kinases, ion channel members and growth factors. Genes encoding regulators of apoptosis, signal transduction and metabolism were altered by the interaction between FGL-treatment and TBI. FGL-treatment in non-injured animals rendered genes regulating signaling, transport and cytoskeleton maintenance significantly increased. Thus, the hypothesis of a putative neuroprotective role of FGL was supported by our findings.
Pedersen
Martin Volmer
MV
Protein Laboratory, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. mets@plab.ku.dk
Helweg-Larsen
Rehannah Borup
RB
Nielsen
Finn Cilius
FC
Berezin
Vladimir
V
Bock
Elisabeth
E
Penkowa
Milena
M
D000818:Animals; D001921:Brain / Q000502:physiology*; D001930:Brain Injuries / Q000235:genetics* / Q000503:physiopathology*; D015536:Down-Regulation / Q000502:physiology; D008297:Male; D019006:Neural Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D015533:Transcriptional Activation / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules