Abstract
A loss of inhibitory interneurons has been reported in the hippocampus following seizure activity in various animal models of epilepsy and in human epileptic tissue. The question of whether particular populations of inhibitory neurons are similarly affected by the chronic block of inhibition tha tresults after tetanus toxin injections directly into the brain has not previously been addressed. In the present study a unilateral intrahippocampal injection of tetanus toxin into the ventral hippocampus was used to produce a chronic epileptic syndrome characterised by brief seizures that recurred intermittently for 6–8 weeks. The results reveal, for the first time, the morphological changes in somatostatin interneurons following tetanus toxin-induced seizures in the rat. A bilateral short-term increase in immunoreactivity of somatostatin neurons is present 1 week after injection. This is accompanied by an increased intensity of somatostatin-immunoreactive axon terminals in the outer molecular layer of the dentate gyrus, which is more marked on the contralateral side. A chronic and significant loss of somatostatin-immunoreactive neurons was noted in the hilus of the dentate gyrus 2 months later. The significance of the chronic loss of the hilar somatostatin neurons in the control of excitatory activity in the dentate gyrus and whether the acute morphological changes are due to a direct action of the toxin on release mechanisms or as a result of seizure activity are discussed.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Babb TL, Kupfer WR, Pretorius JK, Crandall PH, Levesque MF (1991) Synaptic reorganization by mossy fibers in human epileptic fascia dentata. Neuroscience 42: 351–363
Best N, Mitchell J, Baimbridge KG, Wheal HV (1993) Changes in parvalbumin immunoreactive neurons in the rat hippocampus following a kainic acid lesion. Neurosci Lett 155: 1–6
Cavazos JE, Sutula TP (1990) Progressive neuronal loss induced by kindling: a possible mechanism in mossy fiber reorganization and hippocampal sclerosis. Brain Res 527: 1–6
Cavazos JE, Golarai G, Sutula TP (1991) Mossy fiber synaptic reorganization induced by kindling: time course of development, progression and permanence. J Neurosci 11: 2795–2803
Collingridge GL, Thompson PA, Davies J, Mellanby J (1981) In vitro effect of tetanus toxin on GABA release from rat hippocampal slices. J Neurochem 37: 1039–1041
Cornish SM, Mitchell J, Wheal HV (1988) A loss of non pyramidal cells in the kainic acid (KA) lesioned rat hippocampus. J Physiol (Lond) 400: 63P
Davenport CJ, Brown WJ, Babb TL (1990) Sprouting of GABAergic and mossy fiber axons in dentate gyrus following intrahippocampal kainate in the rat. Exp Neurol 109: 180–190
Empson RM, Jefferys JGR (1991) Inhibition in primary and secondary chronic epileptic foci induced by intrahippocampal tetanus toxin. Soc Neurosci Abstr 17: 1441
Empson RM, Amital Y, Jefferys JGR, Gutnick MJ (1993) Injection of tetanus toxin into the neocortex elicits persistent epileptiform activity but only transient impairment of GABA release. Neuroscience 57: 235–239
Freund TF, Ylines A, Miettinen R, Pitkanes A, Lahtinen H, Baimbridge KG, Riekkinen PJ (1992) Pattern of neuronal death in the hippocampus after status epilepticus. Relationship to calcium binding protein content and ischaemic vulnerability. Brain Res Bull 28: 27–38
Hawkins CA, Mellanby J (1987) Limbic epilepsy induced by tetanus toxin: a longitudinal electroencephalographic study. Epilepsia 28: 431–444
Hökfelt T (1991) Neuropeptides in perspective: the last ten years. Neuron 7: 867–879
Houser CR (1991) GABA neurons in seizure disorders; a review of immunocytochemical studies. Neurochem Res 16: 295–308
Jefferys JGR (1989) Chronic epileptic foci in vitro in hippocampal slices from rats with the tetanus toxin epileptic syndrome. J Neurophysiol 62: 458–468
Jefferys JGR, Mitchell P, O'hara L, Hardy J, Jordan SJ, Lynch M, Wadsworth J (1988) Release of excitatory and inhibitory amino acids from hippocampal slices in tetanus toxin chronic epilepsy. Soc Neurosci Abstr 14: 882
Jefferys JGR, Evans BJ, Hughs SA, Williams SF (1992) Neuropathology of the chronic epileptic syndrome induced by intrahippocampal tetanus toxin in rat: preservation of pyramidal cells and incidence of dark cells. Neuropathol Appl Neurobiol 18: 53–70
Johansen FF, Zimmer J, Diemer NH (1987) Early loss of somatostatin neurons in dentate hilus after cerebral ischaemia in the rat precedes CA 1 pyramidal cell loss. Acta Neuropathol (Berl) 73: 110–114
Kessler J, Markowitsch HJ (1983) Different neuropathological effects of intrahippocampal injections of kainic acid and tetanus toxin. Experientia 39: 922–924
Lanerolle NC de, Kim JH, Robbins RJ, Spencer DD (1989) Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. Brain Res 495: 387–395
Lowenstein DH, Thomas MJ, Smith DH, McIntosh TK (1992) Seletive vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus. J Neurosci 12: 4846–4853
Meldrum BS (1975) Epilepsy and-amino butyric acid-mediated inhibition. Int Rev Neurobiol 17: 1–36
Mellanby JH (1989) Elimination of 125I from rat brain after injection of small doses of 125I-labelled tetanus toxin into the hippocampus. Neurosci Lett 36 [Suppl]: S55
Mellanby JH, George G, Robinson A, Thompson P (1977) Epileptiform syndrome in rats produced by injecting tetanus toxin into the hippocampus. J Neurol Neurosurg Psychiatry 40: 404–414
Najlerahim A, Williams SF, Pearson RCA, Jefferys JGR (1992) Increased expression of GAD mRNA during the chronic epileptic syndrome due to intrahippocampal tetanus toxin. Exp Brain Res 90: 332–342
Nitsch C, Goping G, Klatzo I (1989) Preservation of GABAergic perikarya and boutons after transient ischemia in the gerbil hippocampal CA1 field. Brain Res 495: 243–252
Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, Sydney
Represa A, Trembay E, Ben Ari Y (1990). In: Ben Ari Y (ed) Excitatory amino acids and neuronal plasticity. Plenum Press, New York, pp 419–424
Robbins RJ, Brines ML, Kim JH, Adrian T, Lanerolle N de, Welsh S, Spencer D (1991) A selective loss of somatostatin in the hippocampus of patients with temporal lobe epilepsy. Ann Neurol 29: 325–332
Roberts E (1980) Epilepsy and antiepileptic drugs: a speculative synthesis. In: Glaser GH, Penry JK, Woodbury DM (eds) Antiepileptic drugs: mechanism of action. Raven Press, New York, pp 667–713
Schiavo G, Benfenati F, Poulain B, Rossetto O, Polverino de Laureto P, DasGupta BR, Montecucco C (1992) Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359: 832–835
Schwab ME, Suda K, Thoenen H (1979) Selective retrograde transynaptic transfer of protein, tetanus toxin, subsequent to its retrograde axonal transport. J Cell Biol 82: 798–810
Shaw JAG, Perry VH, Mellanby J (1990) Tetanus toxin-induced seizures cause microglial activation in rat hippocampus. Neurosci Lett 120: 66–69
Sloviter RS (1991) Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science 235: 73–76
Sloviter RS (1991) Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the dormant basket cell hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus 1: 41–66
Sloviter RS, Sollas AL, Barbado NM, Laxer KD (1991) Calcium binding protein (calbindin-D28K) and parvalbumin immunocytochemistry in the normal and epileptic human hippocampus. J Comp Neurol 308: 381–396
Sperk G, Wieser R, Widmann R, Singer EA (1986) Kainic acidinduced seizures: changes in somatostatin, substance P and neurotensin. Neuroscience 17: 1117–1126
Sperk G, Marksteiner J, Gruber B, Bellman R, Mahata M, Ortler M (1992) Functional changes in neuropeptide Y and somatostatin containing neurons induced by limbic seizures in the rat. Neuroscience 50: 831–846
Sundstrom LE, Mellanby JH (1990) Tetanus toxin blocks inhibition of granule cells in the dentate gyrus of the urethaneanesthetized rat. Neuroscience 38: 621–627
Sundstrom LE, Mitchell J, Wheal HV (1993) Bilateral reorganisation of mossy fibres in the rat hippocampus after a unilateral intracerebroventricular kainic acid injection. Brain Res 609: 321–326
Sutula T, Cascino G, Cavazos J, Parada I, Ramirez L (1989) Hippocampal synaptic reorganization in partial complex epilepsy: evidence for mossy fiber sprouting in epileptic human temporal lobe. Ann Neurol 26: 321–330
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mitchell, J., Gatherer, M. & Sundstrom, L.E. Loss of hilar somatostatin neurons following tetanus toxin-induced seizures. Acta Neuropathol 89, 425–430 (1995). https://doi.org/10.1007/BF00307647
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00307647