Abstract
Several reports have suggested the involvement of different growth factors in the cascade of events that underlies epileptogenesis. Among these, nerve-growth factor (NGF) and brain-derived neurotrophic factor (BDNF) from the neurotrophin family appear to play a critical role [16]. These neurotrophins are involved in the development of the central nervous system as well as in adult brain plasticity [38, 24]. Neurotrophins bind to receptors of the tyrosine kinase family, and the high affinity receptors for NGF and BDNF are TrkA and TrkB respectively [17]. Expression of both NGF and BDNF and their high affinity receptor messenger RNAs increases in the hippocampus, amygdala and cortex after different forms of convulsive seizures in the rat [4, 3, 14, 19, 18, 28, 34, 12]. In the kindling model of epilepsy, the first electrical stimulation of the hippocampus induces a rapid increase of BDNF mRNA expression in the granule cells of the dentate gyrus, in both the stimulated and the non-stimulated sides [14] (see Lindvall et al., chapter 22 in this volume). After several stage 5 seizures, BDNF mRNA expression is also increased throughout CA l -CA3 pyramidal layer, the hilar region of the dentate gyrus, the amygdala, parietal and piriform cortex [14, 3]. During kindling, a parallel increase of BDNF and trkB mRNAs occurs in the dentate granule cells and suggests an autocrine or paracrine action of BDNF in the hippocampus [3]. However, the physiological significance of the increased expression of neurotrophins remains to be determined and BDNF and NGF could be involved in the neuroplastic processes that either facilitate or inhibit the development of seizures. Recent studies (see Racine et al., chapter 15 in this volume) suggest that over-expression of NGF could promote the occurrence of seizures. In our laboratory, we have investigated the effects of BDNF on epileptogenesis by examining the effects of chronic intracerebral perfusions of recombinant human BDNF on the development of seizures in the kindling model in the rat [23].
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References
Anderson, K.D., Alderson, R.F., Altar, C.A., Distefano, P.S., Corcoran, T.L., Lindsay, R.M. and Wiegand, S.J., Differential distribution of exogenous BDNF, NGF, and NT-3 in the brain corresponds to the relative abundance and distribution of high-affinity and low-affinity neurotrophin receptors, J Comp Neurol, 357 (1995) 296–317.
Barde, Y.A., Trophic factors and neuronal survival, Neuron, 2 (1989) 1525–1534.
Bengzon, J., Kokaia, Z., Ernfors, P., Kokaia, M., Leanza, G., Nilsson, O.G., Persson, H. and Lindvall, O., Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling, Neurosci, 53 (1993) 433–446.
Bengzon, J., Söderström, S., Kokaia, M., Ernfors, P., Persson, H., Ebendal, T. and Lindvall, O., Widespread increase of nerve growth factor protein in the rat forebrain after kindling-induced seizures, Brain Res, 587 (1992) 338–342.
Cavazos, J.E. and Sutula, T.P., Progressive neuronal loss induced by kindling: A possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis, Brain Res., 527 (1990) 1–6.
Colmers, W.F. and Bleakman, D., Effects of neuropeptide Y on the electrical properties of neurons, Trends Neurosci, 17 (1994) 373–379.
Croll, S.D., Wiegand, S.i., Anderson, K.D., Lindsay, R.M. and Nawa, H., Regulation of neuropeptides in adult rat forebrain by the neurotrophins BDNF and NGF, EurJ Neurosci, 6 (1994) 1343–1353.
Danscher, G., Histochemical demonstration of heavy metals. A revised version of the sulphide silver method suitable for both light and electron microscopy, Histochemistry, 71 (1981) 1–16.
Davies, A.M., The role of neurotrophins in the developing nervous system, J Neurobiol, 25 (1994) 1334–1348.
DiStefano, P.S., Friedman, B., Radziejewski, C., Alexander, C., Boland, P., Schick, C.M., Lindsay, R.M. and Wiegand, S.J., The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde axonal transport in peripheral and central neurons, Neuron, 8 (1992) 983–993.
Dragunow, M., Robertson, H.A., Kindling stimulation induces c-fos protein (s) in granule cells of the rat dentate gyrus, Nature, 329, (1987) 441–442.
Elmer, E., Kokaia, M., Kokaia, Z., Ferencz, I. and Lindvall, O., Delayed kindling development after rapidly recurring seizures: Relation to mossy fiber sprouting and neurotrophin, GAP-43 and dynorphin gene expression, Brain Res, 712 (1996) 19–34.
Erickson, J.C., Clegg, K.E. and Palmiter, R.D., Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y, Nature, 381 (1996) 415–418.
Ernfors, R, Bengzon, J., Kokaia, Z., Persson, H. and Lindvall, O., Increased levels of messengers RNAs for neurotrophic factors in the brain during kindling epileptogenesis, Neuron, 7 (1991) 165–176.
Funabashi, T., Sasaki, H. and Kimura, F., Intraventricular injection of antiserum to nerve growth factor delays the development of amygdaloid kindling, Brain Res, 458 (1988) 132–136.
Gall, C., Seizure-induced changes in neurotrophin expression: implications for epilepsy, Experimental Neurology, 124 (1993) 150–166.
Glass, D.J. and Yancopoulos, G.D., The neurotrophins and their receptors, Trends in cell biology, 3 (1993) 262–268.
Humpel, C., Ebdendal, T., Cao, Y. and Olson, L., Pentylenetetrazol seizures increase pro-nerve growth factor-like immunoreactivity in the reticular thalamic nucleus and nerve growth factor mRNA in the dentate gyrus, J Neurosci Res, 35 (1993) 419–427.
Humpel, C., Wetmore, C. and Olson, L., Regulation of brain-derived neurotrophic factor messenger RNA and protein at the cellular level in pentylenetetrazol-induced epileptic seizures, Neurosci, 53 (1993) 909–918.
Jones, K.R., Farinas, I., Backus, C. and Reichardt, L.F., Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development, Cell, 76 (1994) 989–999.
Kokaia, M., Ernfors, P., Kokaia, Z., Elmer, E., Jaenisch, R. and Lindvall, O., Suppressed epileptogenesis in BDNF mutant mice, Exp Neurol, 133 (1995) 215–224.
Korte, M., Carroll, P., Wolf, E., Brem, G., Thoenen, H. and Bonhoeffer, T., Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor, Proc Natl Acad Sci USA, 92 (1995) 8856–8860.
Larmet, Y., Reibel, S., Carnahan, J., Nawa, H., Marescaux, C. and Depaulis, A., Protective effects of brain-derived neurotrophic factor on the development of hippocampal kindling in the rat, Neuroreport, 6 (1995) 1937–1941.
Lindvall, O., Kokaia, Z., Bengzon, J., Elmér, E. and Kokaia, M., Neurotrophins and brain insults, Trends Neurosci, 17 (1994) 490–496.
Marsh, H.N., Scholz, W.K., Lamballe, F., Klein, R., Nanduri, V., Barbacid, M. and Palfrey, H.C., Signal transduction events mediated by the BDNF receptor gp 145trkB in primary hippocampal pyramidal cell culture, Journal of neuroscience, 13 (1993) 4281–4292.
Marty, S., Carroll, R, Cellerino, A., Castren, E., Staiger, V., Thoenen, H. and Lindholm, D., Brain-derived neurotrophic factor promotes the differentiation of various hippocampal nonpyramidal neurons, including Cajal-Retzius cells, in organotypic slice cultures, J Neurosci, 16 (1996) 675–687.
McNamara, J.O., Cellular and molecular basis of epilepsy, J Neurosci, 14 (1994) 3413–3425.
Merlio, J.P., Ernfors, P., Kokaia, Z., Middlemas, D.S., Bengzon, J., Kokaia, M., Smith, M.L., Siesjö, B.K., Hunter, T., Lindvall, O. and Persson, H., Increased production of TrkB protein tyrosine kinase receptor after brain insults, Neuron, 10 (1993) 151–164.
Paxinos, G. and Watson, C., The rat brain in stereotaxic coordinates, Academic Press, Sydney, 1986, pages.
Racine, R.J., Modification of seizure activity by electrical stimulation: II. Motor seizure, Electroencephalogr Clin Neurophysiol, 32 (1972) 281–294.
Rashid, K., Van der Zee, C.E.E.M., Ross, G.M., Chapman, C.A., Stanisz, J., Riopelle, R.J., Racine, R.J. and Fahnestock, M., A nerve growth factor peptide retards seizure development and inhibits neuronal sprouting in a rat model of epilepsy, Proc Natl Acad Sci USA, 92 (1995) 9495–9499.
Rizzi, M., Monno, A., Samanin, R., Sperk, G. and Vezzani, A., Electrical kindling of the hippocampus is associated with functional activation of neuropeptide Y-containing neurons, Eur J Neurosci, 5 (1993) 1534–1538.
Rosen, J.B., Kim, S.Y. and Post, R.M., Differential regional and time course increases in thyrotropin-releasing hormone, neuropeptide Y and enkephalin mRNAs following an amygdala kindled seizure, Mol Brain Res, 27 (1994) 71–80.
Sato, K., Kashihara, K., Morimoto, K. and Hayabara, T., Regional increases in brain-derived neurotrophic factor and nerve growth factor mRNAs during amygdaloid kindling, but not in acidic and basic fibroblast growth factor mRNAs, Epilepsia, 37 (1996) 6–14.
Sutula, T., Cascino, G., Cavazos, J., Parada, I. and Ramirez, L., Mossy fiber synaptic reorganization in the epileptic human temporal lobe, Ann Neurol, 26 (1989) 321–330.
Sutula, T., Xiao-Xian, H., Cavazos, J. and Scott, G., Synaptic reorganization in the hippocampus induced by abnormal functional activity, Science, 239 (1988) 1147–1150.
Tauck, D.L. and Nadler, J.V., Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats, Journal of Neuroscience, 5 (1985) 1016–1022.
Thoenen, H., Neurotrophins and neuronal plasticity, Science, 270 (1995) 593–598.
Tønder, N., Kragh, J., Finsen, B.R., Bolwig, T.G. and Zimmer, J., Kindling induces transient changes in neuronal expression of somatostatin, neuropeptide Y, and calbindin in adult rat hippocampus and fascia dentata, Epilepsia, 35 (1994) 1299–1308.
Van der Zee, C.E.E.M., Rashid, K., Le, K., Moore, K.A., Stanisz, J., Diamond, J., Racine, R.J. and Fahnestock, M., Intraventricular administration of antibodies to nerve growth factor retards kindling and blocks mossy fiber sprouting in adult rats, J Neurosci, 15 (1995) 5316–5323.
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Reibel, S., Larmet, Y., Carnahan, J., Lê, BT., Marescaux, C., Depaulis, A. (1998). Protective Effects of Brain-Derived Neurotrophic Factor in Hippocampal Kindling. In: Corcoran, M.E., Moshé, S.L. (eds) Kindling 5. Advances in Behavioral Biology, vol 48. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5375-5_29
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