Biochemical Studies of Neuronal and Other Cell Types

Brenneman, D E.

Abstract

Cell cultures prepared from fetal mammalian central nerves system were used to study the regulation of neuronal development. Mechanisms which relate to the role of electrical activity during development were investigated. Addition of 0.1 nM vasoactive intestinal peptide (VIP) to dissociated spinal cord cultures resulted in an increase in neuronal survival during electrical blockade. VIP antiserum and receptor blockade with VIP10-28 decreased neuronal survival to a similar extent as treatment with tetrodotoxin. Vasoactive intestinal peptide was shown to act indirectly through non-neuronal background cells to increase neuronal survival during electrical blockade. Conditioned medium obtained from VIP stimulated non-neuronal cultures produced an increase in neuronal survival as compared to that obtained from sister cultures not treated with VIP. Receptor binding studies indicated that VIP sites were present on non-neuronal cultures. Increase in cAMP levels were observed in background cultures treated with 10 nM VIp. We have investigated the possibility that peptide neurotransmitters and neurohormones play a role in the development of their target organ. Early exposure to the neuropeptides was found to permanently affect the expression of neuropeptide receptors, and that this alteration in receptors was of physiological and behavioral importance to the mature animal. For opioid peptides, the developmental effects in rats parallel findings in children exposed in utero to opiate drugs, suggesting that a similar mechanism my operate in humans.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
• Type: Intramural Research (Z01)
• Project #: 1Z01HD000047-16
• Application #: 4693701
• Support Year: 16
• Fiscal Year: 1985

Institution

• Name: U.S. National Inst/Child Hlth/Human Dev
• Country: United States

Publications

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