A single administration of the peptide NAP induces long-term protective changes against the consequences of head injury: gene Atlas array analysis.
The femtomolar-acting eight-amino-acid peptide (NAP), derived from activity-dependent neuroprotective protein (ADNP), provides long-term protection against the deleterious effects of closed head injury (CHI) in mice. Fifteen minutes after injury, mice were divided into two groups, control and NAP-treated and a single subcutaneous injection of NAP or vehicle was administered. A third group served as sham-treated (not subjected to head trauma). Each mouse was assessed for its clinical function, using neurological severity score, at various time intervals following CHI, up to 30-45 d. Total cerebral cortex RNA was prepared from the site of injury of CHI mice, and from parallel regions in peptide-treated and sham brains. RNA was then reversed transcribed to yield radioactive cDNA preparations that were hybridized to Atlas array membranes containing 1200 cDNAs spots. Comparison of sham-treated individual mice showed differential expression levels of at least 15 mRNA species. Furthermore, results indicated that one of the genes that did not change among individuals but specifically increased after CHI and decreased after NAP treatment was the cell surface glycoprotein Mac-1 (CD11B antigen). Thus, Mac-1 is suggested as a marker for the long-term outcome of head injury and as a potential target for NAP protective actions.
Romano
Jacob
J
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Beni-Adani
Liana
L
Nissenbaum
Orlev Levy
OL
Brenneman
Douglas E
DE
Shohami
Esther
E
Gozes
Illana
I
D000818:Animals; D015415:Biomarkers; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D015415:Biomarkers; D016177:Macrophage-1 Antigen; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009842:Oligopeptides; D012333:RNA, Messenger; C425904:davunetide