Skip to main content

Advertisement

SpringerLink
Log in

α-MSH Rescues Neurons from Excitotoxic Cell Death

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

This study investigates the effects of alpha-melanocyte-stimulating hormone (α-MSH), on neurodegeneration, gliosis and changes in the neurotrophic protein brain-derived neurotrophic factor (BDNF) and in pro-inflammatory cytokines, following kainic acid (KA)-induced excitotoxic damage in the rat. Male Sprague-Dawley rats were treated with α-MSH (intraperitoneally, i.p.) at 20 min, and 24 and 48 h following administration of 10 mg/kg KA (i.p.). The animals were sacrificed at 30 min, 4 h, 24 h and 72 h after KA-administration and the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were analysed in samples of hippocampus and hypothalamus. Levels of BDNF were analysed in the hippocampus. Stereological quantification showed a markedly reduced number of viable neurons in the CA1 pyramidal cell layer upon KA-administration as compared to animals injected with vehicle (p < 0.05, 79,587 ±  25,554 vs. 145,254 ± 27,871). The number of viable neurons upon administration of α-MSH was significantly higher than upon KA alone (p < 0.05, 119,776 ± 33,158, KA+α-MSH vs. 79,587 ± 27,554, KA + Saline). Astrocyte activation due to the KA-induced excitotoxicity was reduced, and the KA-induced increase in IL-1β levels was delayed by the treatment with α-MSH. In conclusion, the degree of reduction in cell viability in the hippocampus CA1 pyramidal cell layer upon KA-induced excitotoxicity was similar to that seen previously upon global cerebral ischaemia. Furthermore, the administration of α-MSH resulted in a similar increase in cell viability, supporting the hypothesis that administration of α-MSH has rescuing effects on neurons subjected to excitotoxic insults.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adan, R., & Gispen, W. (1997). Brain melanocortin receptors: From cloning to function. Peptides, 18, 1279–1287.

    Article  PubMed  CAS  Google Scholar 

  • Bazzani, C., Guarini, S., Botticelli, A., Zaffe, D., Tomasi, A., Bini, A., et al. (2001). Protective effect of melanocortin peptides in rat myocardial ischemia. Journal of Pharmacology and Experimental Therapeutics, 297, 1082–1087.

    PubMed  CAS  Google Scholar 

  • Ben-Ari, Y. (1985). Limbic seizure and brain damage produced by kainic acid: Mechanisms and relevance to human temporal lobe epilepsy. Neuroscience, 14, 375–403.

    Article  PubMed  CAS  Google Scholar 

  • Ben-Ari, Y., Tremblay, E., & Ottersen, O. P. (1980). Injections of kainic acid into the amygdaloid complex of the rat: An electrographic, clinical and histological study in relation to the pathology of epilepsy. Neuroscience, 5, 515–528.

    Article  PubMed  CAS  Google Scholar 

  • Bhardwaj, R. S., Schwarz, A., Becher, E., Mahnke, K., Aragane, Y., Schwarz, T., et al. (1996). Proopiomelanocortin-derived peptides induce IL-10 production in human monocytes. Journal of Immunology, 156, 2517–2521.

    CAS  Google Scholar 

  • Cagnin, A., Brooks, D. J., Kennedy, A. M., Gunn, R. N., Myers, R. D., Turkheimer, F. E., et al. (2001). In vivo measurement of activated microglia in dementia. Lancet, 358, 461–467.

    Article  PubMed  CAS  Google Scholar 

  • Cannon, J. G., Tatro, J. B., Reichlin, S., & Dinarello, C. A. (1986). α-melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1. Journal of Immunology, 137, 2232–2236.

    CAS  Google Scholar 

  • Catania, A., Gatti, S., Colombo, A., & Lipton, J. (2004). Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacological Reviews, 56, 1–29.

    Article  PubMed  CAS  Google Scholar 

  • Catania, A., & Lipton, J. (1998). Peptide modulation of fever and inflammation within the brain. Annals of the New York Academy of Sciences, 856, 62–68.

    Article  PubMed  CAS  Google Scholar 

  • Chiao, H., Kohda, Y., McElroy, P., Craig, L., Housini, I., & Star, R. (1997). α-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. Journal of Clinical Investigation, 99, 1165–1172.

    PubMed  CAS  Google Scholar 

  • Cone, R. D. (2005). Anatomy and regulation of the central melanocortin system. Nature Neuroscience, 8, 571–578.

    Article  PubMed  CAS  Google Scholar 

  • Conti, B., Tabarean, I., Andrei, C., & Bartfai, T. (2004). Cytokines and fever. Frontiers in Bioscience, 9, 1433–1449.

    Article  PubMed  CAS  Google Scholar 

  • Coyle, J. T. (1983). Neurotoxic action of kainic acid. Journal of Neurochemistry, 41, 1–11.

    Article  PubMed  CAS  Google Scholar 

  • De Simoni, M. G., Perego, C., Ravizza, T., Moneta, D., Conti, M., Marchesi, F., et al. (2000) Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. European Journal of Neuroscience, 12, 2623–2633.

    Article  PubMed  Google Scholar 

  • De Wied, D., & Jolles, J. (1982). Neuropeptides derived from pro-opiocortin: Behavioural, physiological, and neurochemical effects. Physiological Reviews, 62, 976–1059.

    PubMed  Google Scholar 

  • Delgado, R., Carlin, A., Airaghi, L., Demitri, M., Meda, L., Galimberti, D., et al. (1998). Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia. Journal of Leukocyte Biology, 63, 740–745.

    PubMed  CAS  Google Scholar 

  • Deng, J., Hu, X., Yuen, P. S., & Star, R. A. (2004). α-melanocyte-stimulating hormone inhibits lung injury after renal ischemia/reperfusion. American Journal of Respiratory and Critical Care Medicine, 169, 749–756.

    Article  PubMed  Google Scholar 

  • Eberle, A. (1988). The melanotrophins. Chemistry, physiology and mechanisms of action. Basel: S. Karger AG.

  • Eberle, A., Kriwaczek, V. M., & Schwyzer, R. (1978). Mechanism of α-melanotropin action. Bulletin der Schweizerischen Akademie der Medizinischen Wissenschaften, 34(1–3), 99–111.

    Google Scholar 

  • Eriksson, C., Tehranian, R., Iverfeldt, K., Winblad, B., & Schultzberg, M. (2000a). Increased expression of mRNA encoding interleukin-1β and caspase-1, and the secreted isoform of interleukin-1 receptor antagonist in the rat brain following systemic kainic acid administration. Journal of Neuroscience Research, 60, 266–279.

    Article  CAS  Google Scholar 

  • Eriksson, C., Van Dam, A.-M., Lucassen, P. J., Bol, J. G., Winblad, B., & Schultzberg, M. (1999). Immunohistochemical localization of interleukin-1β, interleukin-1 receptor antagonist and interleukin-1β converting enzyme/caspase-1 in the rat brain after peripheral administration of kainic acid. Neuroscience, 93, 915–930.

    Article  PubMed  CAS  Google Scholar 

  • Eriksson, C., Zou, L. P., Ahlenius, S., Winblad, B., & Schultzberg, M. (2000b). Inhibition of kainic acid induced expression of interleukin-1β and interleukin-1 receptor antagonist mRNA in the rat brain by NMDA-receptor antagonists. Molecular Brain Research, 85, 103–113.

    Article  CAS  Google Scholar 

  • Ferkany, J. W., & Coyle, J. T. (1983). Kainic acid selectively stimulates the release of endogenous excitatory amino acids. Journal of Pharmacology and Experimental Therapeutics, 225, 399–406.

    PubMed  CAS  Google Scholar 

  • Forslin Aronsson, Å., Spulber, S., Popescu, L. M., Winblad, B., Post, C., Oprica, M., et al. (2006). α-melanocyte-stimulating hormone is neuroprotective in rat global cerebral ischemia. Neuropeptides, 40, 65–75.

    Article  PubMed  CAS  Google Scholar 

  • Gantz, I., Shimoto, Y., Konda, Y., Miwa, H., Dickinson, C. J., & Yamada, T. (1994). Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Biochemical and Biophysical Research Communications, 200, 1214–1220.

    Article  PubMed  CAS  Google Scholar 

  • Gary, D. S., Bruce-Keller, A. J., Kindy, M. S., & Mattson, M. P. (1998). Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor. Journal of Cerebral Blood Flow and Metabolism, 18, 1283–1287.

    PubMed  CAS  Google Scholar 

  • Gispen, W. H., Verhaagen, J., & Bar, D. (1994). ACTH/MSH-derived peptides and peripheral nerve plasticity: Neuropathies, neuroprotection and repair. Progress in Brain Research, 100, 223–229.

    Article  PubMed  CAS  Google Scholar 

  • Giuliani, D., Mioni, C., Altavilla, D., Leone, S., Bazzani, C., Minutoli, L., et al. (2006). Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produces neuroprotection in cerebral ischemia. Endocrinology, 147, 1126–1135.

    Article  PubMed  CAS  Google Scholar 

  • Glyn, J., & Lipton, J. (1981). Hypothermic and antipyretic effects of centrally administered ACTH (1–24) and α-melanotropin. Peptides, 2, 177–187.

    Article  PubMed  CAS  Google Scholar 

  • Grilli, M., Goffi, F., Memo, M., & Spano, P. (1996). Interleukin-1β and glutamate activate the nF-kB/Rel binding site from the regulatory region of the amyloid precursor protein gene in primary neuronal cultures. Journal of Biological Chemistry, 271, 15002–15007.

    Article  PubMed  CAS  Google Scholar 

  • Gundersen, H. J., Bagger, P., Bendtsen, T. F., Evans, S. M., Korbo, L., Marcussen, N., et al. (1988). The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS, 96, 857–881.

    Article  PubMed  CAS  Google Scholar 

  • Guo, C. J., Douglas, S. D., Gao, Z., Wolf, B. A., Grinspan, J., Lai, J. P., et al. (2004). Interleukin-1β upregulates functional expression of neurokinin-1 receptor (NK-1R) via NF-κB in astrocytes. Glia, 48, 259–266.

    Article  PubMed  Google Scholar 

  • Hartmeyer, M., Scholzen, T., Becher, E., Bhardwaj, R. S., Schwarz, T., Luger, T. A. (1997). Human dermal microvascular endothelial cells express the melanocortin receptor type 1 and produce increased levels of IL-8 upon stimulation with α-melanocyte-stimulating hormone. Journal of Immunology, 159, 1930–1937.

    CAS  Google Scholar 

  • Hashimoto, K., Watanabe, K., Nishimura, T., Iyo, M., Shirayama, Y., & Minabe, Y. (1998). Behavioral changes and expression of heat shock protein hsp-70 mRNA, brain-derived neurotrophic factor mRNA, and cyclooxygenase-2 mRNA in rat brain following seizures induced by systemic administration of KA. Brain Research, 804, 212–223.

    Article  PubMed  CAS  Google Scholar 

  • Hassoun, H. T., Zou, L., Moore, F. A., Kozar, R. A., Weisbrodt, N. W., & Kone, B. C. (2002). α-melanocyte-stimulating hormone protects against mesenteric ischemia-reperfusion injury. American Journal of Physiology: Gastrointestinal and Liver Physiology, 282, G1059–G1068.

    PubMed  CAS  Google Scholar 

  • Hatten, M. E., Liem, R. K., Shelanski, M. L., & Mason, C. A. (1991). Astroglia in CNS injury. Glia, 4, 233–243.

    Article  PubMed  CAS  Google Scholar 

  • Haycock, J. W., Wagner, M., Morandini, R., Ghanem, G., Rennie, I. G., & Mac Neil, S. (1999). α-melanocyte-stimulating hormone inhibits NF-kappaB activation in human melanocytes and melanoma cells. Journal of Investigative Dermatology, 113, 560–566.

    Article  PubMed  CAS  Google Scholar 

  • Huh, S. K., Lipton, J. M., & Batjer, H. H. (1997). The protective effects of α-melanocyte stimulating hormone on canine brain stem ischemia. Neurosurgery, 40, 132–139.

    Article  PubMed  CAS  Google Scholar 

  • Ichiyama, T., Sakai, T., Catania, A., Barsh, G., Furukawa, S., & Lipton, J. (1999a). Systemically administered α-melanocyte-stimulating peptides inhibit NF-κB activation in experimental brain inflammation. Brain Research, 31, 31–37.

    Article  Google Scholar 

  • Ichiyama, T., Sakai, T., Catania, A., Barsh, G., Furukawa, S., & Lipton, J. (1999b). Inhibition of peripheral NF-κB activation by central action of α-melanocyte-stimulating hormone. Journal of Neuroimmunology, 99, 211–217.

    Article  CAS  Google Scholar 

  • Ichiyama, T., Zhao, H., Catania, A., Furukawa, S., & Lipton, J. M. (1999c). α-melanocyte-stimulating hormone inhibits NF-κB activation and IκB-α degradation in human glioma cells and in experimental brain inflammation. Experimental Neurology, 157, 359–365.

    Article  CAS  Google Scholar 

  • Isackson, P. J., Huntsman, M. M., Murray, K. D., & Gall, C. M. (1991). BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF. Neuron, 6, 937–948.

    Article  PubMed  CAS  Google Scholar 

  • Jacobowitz, D., & O’Donohue, T. (1978). α-Melanocyte stimulating hormone: Immunohistochemical identification and mapping in neurons of rat brain. Proceedings of the National Academy of Sciences of the United States of America, 75, 6300–6304.

    Article  PubMed  CAS  Google Scholar 

  • Katoh-Semba, R., Takeuchi, I. K., Inaguma, Y., Ito, H., & Kato, K. (1999). Brain-derived neurotrophic factor, nerve growth and neurotrophin-3 selcted regions of the rat brain following kainic acid-induced seizure activity. Neuroscience Research, 35, 19–29.

    Article  PubMed  CAS  Google Scholar 

  • Lam, C. W., Getting, S. J., & Perretti, M. (2005). In vitro and in vivo induction of heme oxygenase 1 in mouse macrophages following melanocortin receptor activation. Journal of Immunology, 174, 2297–2304.

    CAS  Google Scholar 

  • Lehtimäki, K. A., Peltola, J., Koskikallio, E., Keränen, T., & Honkaniemi, J. (2003). Expression of cytokines and cytokine receptors in the rat brain after kainic acid-induced seizures. Brain Research. Molecular Brain Research, 110, 253–260.

    Article  PubMed  Google Scholar 

  • Leon, L. R. (2004). Hypothermia in systemic inflammation: Role of cytokines. Frontiers in Bioscience, 9, 1877–1888.

    Article  PubMed  CAS  Google Scholar 

  • Lerner, A. B., & Lee, T. H. (1955). Isolation of homogenous melanocyte stimulating hormone from hog pituitary gland. Journal of the American Chemical Society, 77, 1066–1067.

    Article  CAS  Google Scholar 

  • Lindefors, N., Ballarin, M., Ernfors, P., Falkenberg, T., & Persson, H. (1992). Stimulation of glutamate receptors increases expression of brain-derived neurotrophic factor mRNA in rat hippocampus. Annals of the New York Academy of Sciences, 648, 296–299.

    Article  PubMed  CAS  Google Scholar 

  • Liu, T., McDonnell, P. C., Young, P. R., White, R. F., Siren, A. L., Hallenbeck, J. M., et al. (1993a). Interleukin-1β mRNA expression in ischemic rat cortex. Stroke, 24, 1746–1751.

    CAS  Google Scholar 

  • Liu, Z., Gatt, A., Mikati, M., & Holmes, G. L. (1993b). Effect of temperature on kainic acid-induced seizures. Brain Research, 631, 51–58.

    Article  CAS  Google Scholar 

  • Macaluso, A., McCoy, D., Ceriani, G., Watanabe, T., Biltz, J., Catania, A., et al. (1994). Antiinflammatory influences of a-MSH molecules: Central neurogenic and peripheral actions. Journal of Neuroscience, 14, 2377–2382.

    PubMed  CAS  Google Scholar 

  • Maeda, T., Hashizume, K., & Tanaka, T. (1999). Effect of hypothermia on kainic acid-induced limbic seizures: An electroencephalographic and 14C-deoxyglucose autoradiographic study. Brain Research, 818, 228–235.

    Article  PubMed  CAS  Google Scholar 

  • Mandrika, I., Muceniece, R., & Wikberg, J. E. (2001). Effects of melanocortin peptides on lipopolysaccharide/interferon-γ-induced NF-κB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: Evidence for dual mechanisms of action. Biochemical Pharmacology, 61, 613–621.

    Article  PubMed  CAS  Google Scholar 

  • Manna, S. K., & Aggarwal, B. B. (1998). α-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-κB activation induced by various inflammatory agents. Journal of Immunology, 161, 2873–2880.

    CAS  Google Scholar 

  • Marini, A. M., Jiang, X., Wu, X., Tian, F., Zhu, D., Okagaki, P., et al. (2004). Role of brain-derived neurotrophic factor and NF-κB in neuronal plasticity and survival: From genes to phenotype. Restorative Neurology and Neuroscience, 22, 121–130.

    PubMed  CAS  Google Scholar 

  • Mattson, M. P., Cheng, B., Baldwin, S. A., Smith-Swinowsky, V. L., Keller, J., Geddes, J. W., et al. (1995). Brain injury and tumor necrosis factors induced calbindin D-28k in astrocytes: Evidence for a cytoprotective response. Journal of Neuroscience Research, 42, 357–370.

    Article  PubMed  CAS  Google Scholar 

  • McAllister, A. K., Katz, L. C., & Lo, D. C. (1999). Neurotrophins and synaptic plasticity. Annual Review of Neuroscience, 22, 295–318.

    Article  PubMed  CAS  Google Scholar 

  • Minami, M., Kuraishi, Y., & Satoh, M. (1991). Effects of kainic acid on messenger RNA levels of IL-1β, IL-6, TNF-α and LIF in the rat brain. Biochemical and Biophysical Research Communications, 176, 593–598.

    Article  PubMed  CAS  Google Scholar 

  • Minami, M., Kuraishi, Y., Yabuuchi, K., Yamazaki, A., & Satoh, M. (1992). Induction of interleukin-1β mRNA in rat brain after transient forebrain ischemia. Journal of Neurochemistry, 58, 390–392.

    Article  PubMed  CAS  Google Scholar 

  • Minami, M., Kuraishi, Y., Yamaguchi, T., Nakai, S., Hirai, Y., & Satoh, M. (1990). Convulsants induce interleukin-1β messenger RNA in rat brain. Biochemical and Biophysical Research Communications, 171, 832–837.

    Article  PubMed  CAS  Google Scholar 

  • Morimoto, T., Jiang, J. Y., Yoshimatsu, M., Yoshido, K., & Matsuda, H. (1993). Pathogenic role of glutamate in hyperthermia-induced seizures. Epilepsia, 34, 447–452.

    Article  PubMed  CAS  Google Scholar 

  • Nadjar, A., Combe, C., Laye, S., Tridon, V., Dantzer, R., Amedee, T., et al. (2003). Nuclear factor κB nuclear translocation as a crucial marker of brain response to interleukin-1. A study in rat and interleukin-1 type I deficient mouse. Journal of Neurochemistry, 87, 1024–1036.

    Article  PubMed  CAS  Google Scholar 

  • Nadler, J. V. (1981). Kainic acid as a tool for the study of temporal lobe epilepsy. Life Science, 29, 2031–2042.

    Article  CAS  Google Scholar 

  • Oprica, M., Eriksson, C., & Schultzberg, M. (2003). Inflammatory mechanisms associated with brain damage induced by kainic acid with special reference to the interleukin-1 system. Journal of Cellular and Molecular Medicine, 7, 127–140.

    Article  PubMed  CAS  Google Scholar 

  • Oprica, M., Forslin Aronsson, Å., Post, C., Eriksson, C., Ahlenius, S., Popescu, L. M., et al. (2002). Effects of α-MSH on kainic acid induced changes in core temperature in rats. Peptides, 23, 143–149.

    Article  PubMed  CAS  Google Scholar 

  • Oprica, M., Spulber, S., Post, C., Winblad, B., & Schultzberg M. (2006). The influence of kainic acid on core temperature and cytokine levels in the brain. Cytokine, 35, 77–87.

    Article  PubMed  CAS  Google Scholar 

  • Paxinos, G., & Watson, C. (1986). The rat brain in stereotaxic coordinates. New York: Academic Press.

    Google Scholar 

  • Penkowa, M., Molinero, A., Carrasco, J., & Hidalgo, J. (2001). Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures. Neuroscience, 102, 805–818.

    Article  PubMed  CAS  Google Scholar 

  • Racine, R. J. (1972). Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalography and Clinical Neurophysiology, 32, 281–294.

    Article  PubMed  CAS  Google Scholar 

  • Rajora, N., Boccoli, G., Burns, D., Sharma, S., Catania, A., & Lipton, J. (1997). α-MSH modulates local and circulating tumor necrosis factor-α in experimental brain inflammation. Journal of Neuroscience, 17, 2181–2186.

    PubMed  CAS  Google Scholar 

  • Ravizza, T., Rizzi, M., Perego, C., Richichi, C., Veliskova, J., Moshe, S. L., et al. (2005). Inflammatory response and glia activation in developing rat hippocampus after status epilepticus. Epilepsia, 46, 113–117.

    Article  PubMed  CAS  Google Scholar 

  • Ridet, J. L., Malhotra, S. K., Provat, A., & Gage, F. H. (1997). Reactive astrocytes: Cellular and molecular cues to biological function. Trends in Neuroscience, 20, 570–577.

    Article  CAS  Google Scholar 

  • Robertson, B. A., Gahring, L. C., & Daynes, R. A. (1986). Neuropeptide regulation of interleukin-1 activities: Capacity of α-melanocyte stimulating hormone to inhibit interleukin-1-inducible responses in vivo and in vitro exhibits target cell selectivity. Inflammation, 10, 371–385.

    Article  PubMed  CAS  Google Scholar 

  • Samland, H., Huitron-Resendiz, S., Masliah, E., Criado, J., Henriksen, S. J., & Campbell, I. L. (2003). Profound increase in sensitivity to glutamatergic—but not cholinergic agonist-induced seizures in transgenic mice with astrocyte production of IL-6. Journal of Neuroscience Research, 73, 176–187.

    Article  PubMed  CAS  Google Scholar 

  • Sandman, C. A., Kastin, A. J., & Schally, A. V. (1971). Behavioral inhibition as modified by melanocyte-stimulating hormone (MSH) and light–dark conditions. Physiology & Behavior, 6, 45–48.

    Article  CAS  Google Scholar 

  • Schwartz, L. M., & Osborne, B. A. (1993). Programmed cell death, apoptosis and killer genes. Immunology Today, 14, 582–590.

    Article  PubMed  CAS  Google Scholar 

  • Schwob, J. E., Fuller, T., Price, J. L., & Olney, J. W. (1980). Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid: A histological study. Neuroscience, 5, 991–1014.

    Article  PubMed  CAS  Google Scholar 

  • Sperk, G. (1994). Kainic acid seizures in the rat. Progress in Neurobiology, 42, 1–32.

    Article  PubMed  CAS  Google Scholar 

  • Sperk, G., Lassmann, H., Baran, H., Seitelberger, F., & Hornykiewicz, O. (1985). Kainic acid-induced seizures: Dose-relationship of behavioural, neurochemical and histopathological changes. Brain Research, 338, 289–295.

    Article  PubMed  CAS  Google Scholar 

  • Stoll, G., Jander, S., & Schroeter, M. (1998). Inflammation and glial responses in ischemic brain lesions. Progress in Neurobiology, 56, 149–171.

    Article  PubMed  CAS  Google Scholar 

  • Strand, F. L. (1999). New vistas for melanocortins. Finally, an explanation for their peiotropic functions. Annals of the New York Academy of Sciences, 897, 1–16.

    Article  PubMed  CAS  Google Scholar 

  • Strand, F. L., & Kung, T. T. (1980). ACTH accelerates recovery of neuromuscular function following crushing of peripheral nerve. Peptides, 1, 135–138.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka, T., Tanaka, S., Fujita, T., Takano, K., Fukuda, H., Sako, K., et al. (1992). Experimental complex partial seizures induced by a microinjection of kainic acid into limbic structures. Progress in Neurobiology, 38, 317–334.

    Article  PubMed  CAS  Google Scholar 

  • Touzani, O., Boutin, H., Chuquet, J., & Rothwell, N. (1999). Potential mechanisms of interleukin-1 involvement in cerebral ischaemia. Journal of Neuroimmunology, 100, 203–215.

    Article  PubMed  CAS  Google Scholar 

  • Turski, L., & Kleinrok, Z. (1980). Effects of kainic acid on body temperature of rats: Role of catecholaminergic and serotonergic systems. Psychopharmacology, 71, 35–39.

    Article  PubMed  CAS  Google Scholar 

  • Tyler, W. J., Alonso, M., Bramham, C. R., & Pozzo-Miller, L. D. (2002). From acquisition to consolidation: On the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learning and Memory, 9, 224–237.

    Article  PubMed  Google Scholar 

  • Verhaagen, J., Edwards, P. M., Jennekens, F. G., Schotman, P., & Gispen, W. H. (1986). α-melanocyte-stimulating hormone stimulates the outgrowth of myelinated nerve fibers after peripheral nerve crush. Experimental Neurology, 92, 451–454.

    Article  PubMed  CAS  Google Scholar 

  • Wang, X., Barone, F. C., Aiyar, N. V., & Feuerstein, G. Z. (1997). Interleukin-1 receptor and receptor antagonist gene expression after focal stroke in rats. Stroke, 28, 155–162.

    PubMed  CAS  Google Scholar 

  • Wang, X., Yue, T. L., Barone, F. C., White, R. F., Gagnon, R. C., & Feuerstein, G. Z. (1994). Concomitant cortical expression of TNF-α and IL-1β mRNA following transient focal ischemia. Molecular and Chemical Neuropathology, 23, 103–114.

    PubMed  CAS  Google Scholar 

  • West, M. J., Slomianka, L., & Gundersen, H. J. (1991). Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anatomical Record, 231, 482–497.

    Article  PubMed  CAS  Google Scholar 

  • Wikberg, J. (1999). Melanocortin receptors: Perspectives for novel drugs. European Journal of Pharmacology, 375, 295–310.

    Article  PubMed  CAS  Google Scholar 

  • Yanase, T., Hara, S., Mukai, T., Kuriiwa, F., Iwata, N., Kano, S., et al. (1998). Characterization of temperature rise of the brain and the rectum following intracerebroventricular administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and kainate in rats. Brain Research, 798, 304–310.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neurodegeneration and Neuroinflammation, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, SE-141 86, Stockholm, Sweden

    Åsa Forslin Aronsson, Stefan Spulber, Mircea Oprica, Bengt Winblad, Claes Post & Marianne Schultzberg

  2. Aprea AB, Karolinska Institutet, Fogdevreten 2B, SE-171 77, Stockholm, Sweden

    Claes Post

Authors
  1. Åsa Forslin Aronsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefan Spulber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mircea Oprica
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bengt Winblad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Claes Post
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marianne Schultzberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefan Spulber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Forslin Aronsson, Å., Spulber, S., Oprica, M. et al. α-MSH Rescues Neurons from Excitotoxic Cell Death. J Mol Neurosci 33, 239–251 (2007). https://doi.org/10.1007/s12031-007-0019-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-007-0019-2

Keywords

Search

Navigation