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. 1995 Oct 10;92(21):9495–9499. doi: 10.1073/pnas.92.21.9495

A nerve growth factor peptide retards seizure development and inhibits neuronal sprouting in a rat model of epilepsy.

K Rashid 1, C E Van der Zee 1, G M Ross 1, C A Chapman 1, J Stanisz 1, R J Riopelle 1, R J Racine 1, M Fahnestock 1
PMCID: PMC40828  PMID: 7568161

Abstract

Kindling, an animal model of epilepsy wherein seizures are induced by subcortical electrical stimulation, results in the upregulation of neurotrophin mRNA and protein in the adult rat forebrain and causes mossy fiber sprouting in the hippocampus. Intraventricular infusion of a synthetic peptide mimic of a nerve growth factor domain that interferes with the binding of neurotrophins to their receptors resulted in significant retardation of kindling and inhibition of mossy fiber sprouting. These findings suggest a critical role for neurotrophins in both kindling and kindling-induced synaptic reorganization.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altar C. A., Burton L. E., Bennett G. L., Dugich-Djordjevic M. Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):281–285. doi: 10.1073/pnas.88.1.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bengzon J., Söderström S., Kokaia Z., Kokaia M., Ernfors P., Persson H., Ebendal T., Lindvall O. Widespread increase of nerve growth factor protein in the rat forebrain after kindling-induced seizures. Brain Res. 1992 Aug 7;587(2):338–342. doi: 10.1016/0006-8993(92)91016-8. [DOI] [PubMed] [Google Scholar]
  3. Cavazos J. E., Das I., Sutula T. P. Neuronal loss induced in limbic pathways by kindling: evidence for induction of hippocampal sclerosis by repeated brief seizures. J Neurosci. 1994 May;14(5 Pt 2):3106–3121. doi: 10.1523/JNEUROSCI.14-05-03106.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chao M. V. Neurotrophin receptors: a window into neuronal differentiation. Neuron. 1992 Oct;9(4):583–593. doi: 10.1016/0896-6273(92)90023-7. [DOI] [PubMed] [Google Scholar]
  5. Coughlin M. D., Collins M. B. Nerve growth factor-independent development of embryonic mouse sympathetic neurons in dissociated cell culture. Dev Biol. 1985 Aug;110(2):392–401. doi: 10.1016/0012-1606(85)90098-3. [DOI] [PubMed] [Google Scholar]
  6. Danscher G. Histochemical demonstration of heavy metals. A revised version of the sulphide silver method suitable for both light and electronmicroscopy. Histochemistry. 1981;71(1):1–16. doi: 10.1007/BF00592566. [DOI] [PubMed] [Google Scholar]
  7. Drinkwater C. C., Barker P. A., Suter U., Shooter E. M. The carboxyl terminus of nerve growth factor is required for biological activity. J Biol Chem. 1993 Nov 5;268(31):23202–23207. [PubMed] [Google Scholar]
  8. Eide F. F., Lowenstein D. H., Reichardt L. F. Neurotrophins and their receptors--current concepts and implications for neurologic disease. Exp Neurol. 1993 Jun;121(2):200–214. doi: 10.1006/exnr.1993.1087. [DOI] [PubMed] [Google Scholar]
  9. Ernfors P., Bengzon J., Kokaia Z., Persson H., Lindvall O. Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis. Neuron. 1991 Jul;7(1):165–176. doi: 10.1016/0896-6273(91)90084-d. [DOI] [PubMed] [Google Scholar]
  10. Ernfors P., Ibáez C. F., Ebendal T., Olson L., Persson H. Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5454–5458. doi: 10.1073/pnas.87.14.5454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ernfors P., Wetmore C., Olson L., Persson H. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron. 1990 Oct;5(4):511–526. doi: 10.1016/0896-6273(90)90090-3. [DOI] [PubMed] [Google Scholar]
  12. Funabashi T., Sasaki H., Kimura F. Intraventricular injection of antiserum to nerve growth factor delays the development of amygdaloid kindling. Brain Res. 1988 Aug 16;458(1):132–136. doi: 10.1016/0006-8993(88)90504-5. [DOI] [PubMed] [Google Scholar]
  13. Gall C. M., Isackson P. J. Limbic seizures increase neuronal production of messenger RNA for nerve growth factor. Science. 1989 Aug 18;245(4919):758–761. doi: 10.1126/science.2549634. [DOI] [PubMed] [Google Scholar]
  14. Goddard G. V., McIntyre D. C., Leech C. K. A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol. 1969 Nov;25(3):295–330. doi: 10.1016/0014-4886(69)90128-9. [DOI] [PubMed] [Google Scholar]
  15. Ibáez C. F., Ebendal T., Persson H. Chimeric molecules with multiple neurotrophic activities reveal structural elements determining the specificities of NGF and BDNF. EMBO J. 1991 Aug;10(8):2105–2110. doi: 10.1002/j.1460-2075.1991.tb07743.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klein R., Conway D., Parada L. F., Barbacid M. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain. Cell. 1990 May 18;61(4):647–656. doi: 10.1016/0092-8674(90)90476-u. [DOI] [PubMed] [Google Scholar]
  17. Lamballe F., Klein R., Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991 Sep 6;66(5):967–979. doi: 10.1016/0092-8674(91)90442-2. [DOI] [PubMed] [Google Scholar]
  18. Lindvall O., Kokaia Z., Bengzon J., Elmér E., Kokaia M. Neurotrophins and brain insults. Trends Neurosci. 1994 Nov;17(11):490–496. doi: 10.1016/0166-2236(94)90139-2. [DOI] [PubMed] [Google Scholar]
  19. Longo F. M., Vu T. K., Mobley W. C. The in vitro biological effect of nerve growth factor is inhibited by synthetic peptides. Cell Regul. 1990 Jan;1(2):189–195. doi: 10.1091/mbc.1.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McDonald N. Q., Lapatto R., Murray-Rust J., Blundell T. L. X-ray crystallographic studies on murine nerve growth factor. J Cell Sci Suppl. 1990;13:19–30. doi: 10.1242/jcs.1990.supplement_13.4. [DOI] [PubMed] [Google Scholar]
  21. Merlio J. P., Ernfors P., Jaber M., Persson H. Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system. Neuroscience. 1992 Dec;51(3):513–532. doi: 10.1016/0306-4522(92)90292-a. [DOI] [PubMed] [Google Scholar]
  22. Merlio J. P., Ernfors P., Kokaia Z., Middlemas D. S., Bengzon J., Kokaia M., Smith M. L., Siesjö B. K., Hunter T., Lindvall O. Increased production of the TrkB protein tyrosine kinase receptor after brain insults. Neuron. 1993 Feb;10(2):151–164. doi: 10.1016/0896-6273(93)90307-d. [DOI] [PubMed] [Google Scholar]
  23. Nanduri J., Vroegop S. M., Buxser S. E., Neet K. E. Immunological determinants of nerve growth factor involved in p140trk (Trk) receptor binding. J Neurosci Res. 1994 Mar 1;37(4):433–444. doi: 10.1002/jnr.490370402. [DOI] [PubMed] [Google Scholar]
  24. Patil N., Lacy E., Chao M. V. Specific neuronal expression of human NGF receptors in the basal forebrain and cerebellum of transgenic mice. Neuron. 1990 Mar;4(3):437–447. doi: 10.1016/0896-6273(90)90056-l. [DOI] [PubMed] [Google Scholar]
  25. Phillips H. S., Hains J. M., Laramee G. R., Rosenthal A., Winslow J. W. Widespread expression of BDNF but not NT3 by target areas of basal forebrain cholinergic neurons. Science. 1990 Oct 12;250(4978):290–294. doi: 10.1126/science.1688328. [DOI] [PubMed] [Google Scholar]
  26. Pioro E. P., Cuello A. C. Distribution of nerve growth factor receptor-like immunoreactivity in the adult rat central nervous system. Effect of colchicine and correlation with the cholinergic system--I. Forebrain. Neuroscience. 1990;34(1):57–87. doi: 10.1016/0306-4522(90)90304-m. [DOI] [PubMed] [Google Scholar]
  27. Racine R. J. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281–294. doi: 10.1016/0013-4694(72)90177-0. [DOI] [PubMed] [Google Scholar]
  28. Represa A., Ben-Ari Y. Kindling is associated with the formation of novel mossy fibre synapses in the CA3 region. Exp Brain Res. 1992;92(1):69–78. doi: 10.1007/BF00230384. [DOI] [PubMed] [Google Scholar]
  29. Represa A., Le Gall La Salle G., Ben-Ari Y. Hippocampal plasticity in the kindling model of epilepsy in rats. Neurosci Lett. 1989 May 8;99(3):345–350. doi: 10.1016/0304-3940(89)90471-0. [DOI] [PubMed] [Google Scholar]
  30. Represa A., Robain O., Tremblay E., Ben-Ari Y. Hippocampal plasticity in childhood epilepsy. Neurosci Lett. 1989 May 8;99(3):351–355. doi: 10.1016/0304-3940(89)90472-2. [DOI] [PubMed] [Google Scholar]
  31. Sobreviela T., Clary D. O., Reichardt L. F., Brandabur M. M., Kordower J. H., Mufson E. J. TrkA-immunoreactive profiles in the central nervous system: colocalization with neurons containing p75 nerve growth factor receptor, choline acetyltransferase, and serotonin. J Comp Neurol. 1994 Dec 22;350(4):587–611. doi: 10.1002/cne.903500407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Springer J. E., Loy R. Intrahippocampal injections of antiserum to nerve growth factor inhibit sympathohippocampal sprouting. Brain Res Bull. 1985 Dec;15(6):629–634. doi: 10.1016/0361-9230(85)90212-6. [DOI] [PubMed] [Google Scholar]
  33. Sutula T. P., Golarai G., Cavazos J. Assessing the functional significance of mossy fiber sprouting. Epilepsy Res Suppl. 1992;7:251–259. [PubMed] [Google Scholar]
  34. Sutula T., Cascino G., Cavazos J., Parada I., Ramirez L. Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann Neurol. 1989 Sep;26(3):321–330. doi: 10.1002/ana.410260303. [DOI] [PubMed] [Google Scholar]
  35. Sutula T., He X. X., Cavazos J., Scott G. Synaptic reorganization in the hippocampus induced by abnormal functional activity. Science. 1988 Mar 4;239(4844):1147–1150. doi: 10.1126/science.2449733. [DOI] [PubMed] [Google Scholar]
  36. Van der Zee C. E., Fawcett J., Diamond J. Antibody to NGF inhibits collateral sprouting of septohippocampal fibers following entorhinal cortex lesion in adult rats. J Comp Neurol. 1992 Dec 1;326(1):91–100. doi: 10.1002/cne.903260108. [DOI] [PubMed] [Google Scholar]
  37. Van der Zee C. E., Rashid K., Le K., Moore K. A., Stanisz J., Diamond J., Racine R. J., Fahnestock M. Intraventricular administration of antibodies to nerve growth factor retards kindling and blocks mossy fiber sprouting in adult rats. J Neurosci. 1995 Jul;15(7 Pt 2):5316–5323. doi: 10.1523/JNEUROSCI.15-07-05316.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yamamori T. Molecular mechanisms for generation of neural diversity and specificity: roles of polypeptide factors in development of postmitotic neurons. Neurosci Res. 1992 Jan;12(5):545–582. doi: 10.1016/0168-0102(92)90064-j. [DOI] [PubMed] [Google Scholar]

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