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Repeated electroconvulsive shocks cause transient changes in rat hippocampal somatostatin and neuropeptide Y immunoreactivity and mRNA in situ hybridization signals

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Abstract

Increased levels of somatostatin (SS) and neuropeptide Y (NPY) have been demonstrated in the hippocampal formation after kindling. The increase might be specifically associated with kindling, or be an effect of repeated seizures per se. In order to separate these two components we studied the effects of repeated electroconvulsive shocks (ECS) on hippocampal SS-like and NPY-like immunoreactivity and SS mRNA and NPY mRNA in situ hybridization. ECS elicit seizures without having a demonstrable kindling effect. Rats were subjected to 10, 20, or 36 ECS (50 mA, 0.5 s), given as one shock per day, 5 days per week. One, 2 and 30 days after the last ECS, the rats were killed, together with sham-treated control rats, and processed for immunocytochemistry and non-radioactive in situ hybridization. There was a bilateral increase in SS-like and NPY-like immunoreactivity 1 and 2 days after the last ECS in the outer part of the dentate molecular layer. This is the terminal field of the hilar SS-containing and NPY-containing neurons, which displayed both increased immunoreactivity and hybridization signal of the cell bodies. There was also a bilateral de novo expression of NPY-like immunoreactivity in the mossy fiber system, but this was not accompanied by the appearance of a detectable NPY hybridization signal over the parent dentate granule cell bodies. The increase in SS-like immunoreactivity and hybridization signal was most pronounced in the rats that had received the largest number of ECS. This was not observed for the NPY-like immunoreactivity and hybridization signal, where the increase appeared similar after 10, 20 and 36 ECS. One month after the last ECS, both the SS-like and NPY-like immunoreactivity and the in situ hybridization signals had decreased towards normal levels. Since increased SS and NPY levels are also induced by repeated ECS, these changes are accordingly not specific to kindling-induced seizures. In a second experiment, the perforant path to the fascia dentata was transected 1 month prior to the ECS treatment. Removal of such major afferent input did not abolish the ECS-induced increase in hippocampal SS-like and NPY-like immunoreactivity, suggesting that the neuropeptide changes were not caused by afferent stimulation via the perfant path fibers, but rather may be an effect of direct electrical activation of the relevant cells.

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References

  • Andersen P, Bliss TVP, Skrede KK (1971) Lamellar organization of hippocampal excitatory pathways. Exp Brain Res 13:222–238.

    Google Scholar 

  • Bakst I, Avendano C, Morrison JH, Amaral DG (1986) An experintal analysis of the origins of somatostatin-like immunoreactivity in the dentate gyrus of the rat. J Neurosci 6:1452–1462.

    Google Scholar 

  • Bendotti C, Vezzani A, Serafini R, Servadio A, Rivolta R, Samanin R (1991) Increased preproneuropeptide Y mRNA in the rat hippocampus during the development of hippocampal kindling: comparison with the expression of preprosomatostatin mRNA. Neurosci Lett 132:175–178.

    Google Scholar 

  • Bleakman D, Harrison NL, Colmers WF, Miller RJ (1992) Investigations into neuropeptide Y mediated presynaptic inhibition in cultured hippocampal neurons of the rat. Br J Pharmacol 107:334–340.

    Google Scholar 

  • Brown MR, Fisher LA, Sawchenko PE, Swanson LW, Vale WW (1983) Biological effects of cysteamine: relationship to somatostatin depletion. Regul Pept 5:163–179.

    Google Scholar 

  • Chan-Palay V (1987) Somatostatin immunoreactive neurons in human hippocampus and cortex shown by immunogold/silver intensification on vibratome sections. Coexistence with neuropeptide Y neurons, and effects in Alzheimer-type dementia. J Comp Neurol 260:201–223.

    Google Scholar 

  • Cole AJ, Saffen DW, Barban JM, Worley PF (1989) Rapid increase of immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 340:474–476.

    Google Scholar 

  • Cole AJ, Sawsan A-S, Saffen DW, Baraban JM, Worley PF (1990) Rapid rise in transcription factor mRNAs in rat brain after electroshock-induced seizures. J Neurochem 55:1920–1927.

    Google Scholar 

  • Colmers WF, Klapstein GJ, Fournier A, St Pierre S, Treherne KA (1991) Presynaptic inhibition by neuropeptide Y in the rat hippocampal slice in vitro is mediated by a Y2 receptor. Br J Pharmacol 102:41–44.

    Google Scholar 

  • Cottrell GA, Robertson HA (1986) Induction and suppression of seizures by cysteamine in hippocampal kindled rats. Brain Res 365:393–396.

    Google Scholar 

  • Daval J-L, Nakajima T, Gleiter CH, Post RM, Marangos PJ (1989) Mouse brain c-fos mRNA distribution following a single electroshock. J Neurochem 52:1954–1957.

    Google Scholar 

  • Finsen B, Tender N, Augood S, Zimmer J (1992) Somatostatin and neuropeptide Y in organotypic slice cultures of the rat hippocampus: an immunocytochemical and in situ hybridization study. Neuroscience 47:105–113.

    Google Scholar 

  • Goddard GV (1967) Development of epileptic seizures through brain stimulation of low intensity. Nature 214:1020.

    Google Scholar 

  • Goddard GV, McIntyre DC, Leech CK (1969) A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 25:295–330.

    Article  CAS  PubMed  Google Scholar 

  • Haas HL, Herman A, Greene RW, Chan-Palay V (1987) Action and location of neuropeptide tyrosine (Y) on hippocampal neurons of the rat in slice preparations. J Comp Neurol 257:208–215.

    Google Scholar 

  • Havlicek V, Friesen HG (1979) Comparison of behavioural effects of somatostatin and beta-endorphin in animals. In: Collu E, Durcharme JG, Barbeau A and Rochefort (eds) Central nervous system effect of hypothalamic hormonens and other peptides. Raven Press, New York, pp 381–402.

    Google Scholar 

  • Heilig M, Widerlöv E (1990) Neuropeptide Y: an overview of central distribution, functional aspects, and possible involvement in neuropsychiatric illness. Acta Psychiatr Scand 82:95–114.

    Google Scholar 

  • Higuchi T, Sikand GS, Kato N, Wada JA, Friesen HG (1983) Profound suppression of kindled seizures by cysteamine: a possible role of somatostatin to kindled seizures. Brain Res 288:359–362.

    Google Scholar 

  • Higuchi T, Shah KR, Sikand GS, West M, Friesen HG (1984a) Changes in immunoreactive somatostatin in brain following lidocaine-induced kindling in rat. Neuropharmacology 23:1311–1314.

    Google Scholar 

  • Higuchi T, Kokubu T, Sikand GS, Wada JA, Friesen HG (1984b) A study of somatostatin receptors in amygdala-kindled rat brain. J Neurochem 43:1271–1276.

    Google Scholar 

  • Hjort-Simonsen A (1972) Projection of the lateral part of the entorhinal area to the hippocampus and fascia dentata. J Comp Neurol 146:219–232.

    Google Scholar 

  • Ioffe S, Havlicek V, Friesen H, Chernick V (1978) Effect of somatostatin (SRIF) and l-glutamate on neurons of the sensorimotor cortex in awake habituated rabbits. Brain Res 153:414–418.

    Google Scholar 

  • Kato N, Higuchi T, Friesen H, Wada JA (1983) Changes of immunoreactive somatostatin and beta-endorphin content in rat brain after amygdaloid kindling. Life Sci 32:2415–2422.

    Google Scholar 

  • Kiyama H, Emson PC (1990) Distribution of somatostatin mRNA in the rat nervous system as visualized by a novel non-radioactive in situ hybridization histochemistry procedure. Neuroscience 38:223–244.

    Google Scholar 

  • Kosaka T, Wu J-Y, Benoit R (1988) GABAergic neurons containing somatostatin-like immunoreactivity in the rat hippocampus and dentate gyrus. Exp Brain Res 71:388–398.

    Google Scholar 

  • Köhler C, Eriksson LG, Davies S, Chan-Palay V (1986) Neuropeptide Y innervation of the hippocampal region in the rat and monkey brain. J Comp Neurol 244:384–400.

    Google Scholar 

  • Köhler C, Eriksson LG, Davies S, Chan-Palay V (1987) Co-localization of neuropeptide tyrosine and somatostatin immunoreactivity in neurons of individual subfields of rat hippocampal region. Neurosci Lett 78:1–6.

    Google Scholar 

  • Kragh J, Bolwig TG, Barry DI (1987) Does electroconvulsive shock have a kindling effect in rats? Eur J Clin Invest 17:218 (II) A 38.

    Google Scholar 

  • Larhammar D, Ericsson A, Persson H (1987) Structure and expression of the rat neuropeptide Y gene. Proc Natl Acad Sci USA 84:2068–2072.

    Google Scholar 

  • Marksteiner J, Sperk G (1988) Concomitant increase of somatostatin, neuropeptide Y and glutamate decarboxylase in the frontal cortex of rats with decreased seizure threshold. Neuroscience 26:379–385.

    Google Scholar 

  • Marksteiner J, Lassmann H, Saria A, Humpel C, Meyer DK, Sperk G (1990) Neuropeptide levels after pentylenetetrazol kindling in the rat. Eur J Neurosci 2:98–103.

    Google Scholar 

  • McNamara JO, Byrne MC, Dasheiff RM, Fitz JG (1980) The kindling model of epilepsy. A review. Prog Neurobiol 15:139–159.

    Google Scholar 

  • Orzi F, Zoli M, Passarelli F, Ferraguti F, Fieschi C, Agnati LF (1990) Repeated electroconvulsive shock increases glial fibrillary acidic protein, ornithine decarboxylase, somatostatin and cholecystokinin immunoreactivities in the hippocampal formation of the rat. Brain Res 533:223–231.

    Google Scholar 

  • Perlin JB, Lothman EW, Geary WA (1987) Somatostatin augments the spread of limbic seizures from the hippocampus. Ann Neurol 21:475–480.

    Google Scholar 

  • Pitkänen A, Jolkkonen J, Sirviö J, Riekkinen P (1988) Somatostatin-like immunoreactivity and somatostatin receptor binding in rat brain in pentylenetetrazol-induced kindling. Peptides 9:105–107.

    Google Scholar 

  • Pitkänen A, Beal MF, Sirviö J, Swartz KJ, Männistö PT, Riekkinen PJ (1989a) Somatostatin, neuropeptide Y, GABA and cholinergic enzymes in brain of pentylenetetrazol-kindled rats. Neuropeptides 14:197–207.

    Google Scholar 

  • Pitkänen A, Hyttinen JM, Riekkinen PJ (1989b) Effect of cysteamine on somatostatin-like immunoreactivity in the amygdalakindled rat brain. Neuropeptides 14:11–16.

    Google Scholar 

  • Post RM, Putnam F, Uhde TW, Weiss SRB (1986) Electroconvulsive therapy as an anticonvulsant. Implications for its mechanism of action in affective illness. Ann NY Acad Sci 462:376–388.

    Google Scholar 

  • Racine RJ (1978) Kindling the first decade. Neurosurgery 3:234–252.

    Google Scholar 

  • Riekkinen PJ, Pitkanen A (1990) Somatostatin and epilepsy. Metabolism 39:112–115.

    Google Scholar 

  • Sagar SM, Landry D, Millard WJ, Badger TM, Arnold MA, Martin JB (1982) Depletion of somatostatin-like immunoreactivity in the rat central nervous system by cysteamine. J Neurosci 2:225–231.

    Google Scholar 

  • Shinoda H, Schwartz JP, Nadi NS (1989) Amygdaloid kindling of rats increases preprosomatostatin mRNA and somatostatin without affecting glutamic acid decarboxylase (GAD) mRNA or GAD. Mol Brain Res 5:243–246.

    Google Scholar 

  • Shinoda H, Nadi NS, Schwartz JP (1991) Alterations in somatostatin and proenkephalin mRNA in response to a single amygdaloid stimulation versus kindling. Mol Brain Res 11:221–226.

    Google Scholar 

  • Stenfors C, Thodorsson E, Mathé AA (1989) Effect of repeated electroconvulsive treatment on regional concentrations of tachykinins, neurotensin, vasoactive intestinal polypeptide, neu-ropeptide Y, and galanin in rat brain. J Neurosci Res 24:445–450.

    Google Scholar 

  • Sternberger LA (1979) Immunocytochemistry. Wiley, New York.

    Google Scholar 

  • Steward O (1976) Topographic organization of the projection from the entorhinal area to the hippocampal formation of the rat. J Comp Neurol 167:285–314.

    Google Scholar 

  • Tavianini MA, Hayes PE, Magazin MC, Minth CD, Dixon JE (1984) Isolation, characterization, and DNA sequence of the rat somatostatin gene. J Biol Chem 259:11798–11803.

    Google Scholar 

  • Wada JA, Sato M, Corcoran ME (1974) Persistent seizure susceptibility and recurrent spontaneous seizures in kindled cats. Epilepsia 15:465–478.

    Google Scholar 

  • Wahlestedt C, Blendy JA, Kellar KJ, Heilig M, Widerlöv E, Ekman R (1990) Electroconvulsive shocks increase the concentration of neocortical and hippocampal neuropeptide Y (NPY)-like immunoreactivity in the rat. Brain Res 507:65–68.

    Google Scholar 

  • Wanscher B, Kragh J, Barry DI, Bolwig T, Zimmer J (1990) Increased somatostatin and enkephalin-like immunoreactivity in the rat hippocampus following hippocampal kindling. Neurosci Lett 118:33–36.

    Google Scholar 

  • Widerlöv E, Lindstrom LH, Wahlestedt C, Ekman R (1988) Neuropeptide Y and peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively. J Psychiatr Res 22:66–79.

    Google Scholar 

  • Zimmer J, Sunde N (1984) Neuropeptides and astroglia in intracerebral hippocampal transplants: an immunohistochemical study in the rat. J Comp Neurol 227:331–347.

    Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Laboratory for Experimental Neuropsychiatry, 6234, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen Ø, Denmark

    J. Kragh & T. G. Bolwig

  2. PharmaBiotec Research Centre, Institute of Neurobiology, University of Aarhus, Aarhus, Denmark

    N. Tønder

  3. PharmaBiotec Research Centre, Department of Anatomy, Institute of Medical Biology, University of Odense, Odense, Denmark

    N. Tønder, B. R. Finsen & J. Zimmer

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  1. J. Kragh
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  2. N. Tønder
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  3. B. R. Finsen
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  4. J. Zimmer
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  5. T. G. Bolwig
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Kragh, J., Tønder, N., Finsen, B.R. et al. Repeated electroconvulsive shocks cause transient changes in rat hippocampal somatostatin and neuropeptide Y immunoreactivity and mRNA in situ hybridization signals. Exp Brain Res 98, 305–313 (1994). https://doi.org/10.1007/BF00228418

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  • DOI: https://doi.org/10.1007/BF00228418

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