Neuropeptides were studied as both regulators of activity-related neurodevelopment and as substances that were themselves regulated by electrical activity. Primary cell culture preparations from the mammalian central nervous system were employed. Vasoactive intestinal peptide was shown to act as a secretagogue for the following from rat cortical astrocytes: an interleukin-I-like substance and protease nexin I. A reversible down regulation of mRNA for VIP was observed in spinal cord cultures that were electrically blocked with tetrodotoxin. This activity-related gene regulation of VIP was attenuated with active phorbol ester or exogenous VIP. A novel antagonist to VIP, when administered to developing rats, was found to produce deficits in complex motor behaviors without delays in the occurrence of developmental milestones. Dystrophic neurons were observed within deep layers of cerebral cortex of developing rats which had been treated with the VIP antagonist. In mature rats, the VIP antagonist was shown to produce cognitive impairment as assessed by performance in the Morris water maze. The regional specificity for the antagonist was demonstrated in that VIP receptors located in lymph nodes, superior cervical ganglion, gut, lung and pancreas were not responsive, whereas those in spinal cord, hippocampus and cerebral cortex were potently inhibited. Northern blots of mRNA were probed with random-primed DNA from the alpha-2-D, alpha-2-A and alpha-1-B adrenergic receptor cDNAs. A unique regional and ontogenic expression was observed for these three subtypes of alpha receptors present in rat brain and other tissues.

Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
1990
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Romano, Jacob; Beni-Adani, Liana; Nissenbaum, Orlev Levy et al. (2002) A single administration of the peptide NAP induces long-term protective changes against the consequences of head injury: gene Atlas array analysis. J Mol Neurosci 18:37-45
Steingart, Ruth A; Heldenberg, Eitan; Pinhasov, Albert et al. (2002) A vasoactive intestinal peptide receptor analog alters the expression of homeobox genes. Life Sci 71:2543-52
Leker, Ronen R; Teichner, Angella; Grigoriadis, Nikolas et al. (2002) NAP, a femtomolar-acting peptide, protects the brain against ischemic injury by reducing apoptotic death. Stroke 33:1085-92
Spong, C Y; Abebe, D T; Gozes, I et al. (2001) Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome. J Pharmacol Exp Ther 297:774-9
Servoss, S J; Lee, S J; Gibney, G et al. (2001) IGF-I as a mediator of VIP/activity-dependent neurotrophic factor-stimulated embryonic growth. Endocrinology 142:3348-53
Porter, A E; Auth, J; Prince, M et al. (2001) Optimization of cytokine stability in stored amniotic fluid. Am J Obstet Gynecol 185:459-62
Beni-Adani, L; Gozes, I; Cohen, Y et al. (2001) A peptide derived from activity-dependent neuroprotective protein (ADNP) ameliorates injury response in closed head injury in mice. J Pharmacol Exp Ther 296:57-63
Ashur-Fabian, O; Giladi, E; Furman, S et al. (2001) Vasoactive intestinal peptide and related molecules induce nitrite accumulation in the extracellular milieu of rat cerebral cortical cultures. Neurosci Lett 307:167-70
Zamostiano, R; Pinhasov, A; Gelber, E et al. (2001) Cloning and characterization of the human activity-dependent neuroprotective protein. J Biol Chem 276:708-14
Zia, H; Leyton, J; Casibang, M et al. (2000) (N-stearyl, norleucine17) VIP hybrid inhibits the growth of pancreatic cancer cell lines. Life Sci 66:379-87

Showing the most recent 10 out of 19 publications