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Abstract:

The functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1β (IL-1β) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1β in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1β in the adult rat SN using a recombinant adenovirus expressing IL-1β. The chronic expression of IL-1β for 60 days induced dopaminergic cell death in the SN and unilateral akinesia starting only at 21 days post-injection. Microglial cell activation and inflammatory cell infiltrate were associated with dopaminergic cell death and motor disabilities. Astrocytic activation was delayed and associated with scar formation. The chronic expression of a single proinflammatory cytokine as IL-1β in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1β per se is able to mediate inflammatory-mediated toxic effects in the SN if its expression is sustained. This model will be helpful to identify possible therapeutic targets related to inflammation-derived neurodegeneration in the SN. © 2006 Elsevier Inc. All rights reserved.

Registro:

Documento: Artículo
Título:Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra
Autor:Ferrari, C.C.; Pott Godoy, M.C.; Tarelli, R.; Chertoff, M.; Depino, A.M.; Pitossi, F.J.
Filiación:Institute Leloir, IIBBA-CONICET, FBMC-FCEyN, Ave. Patricias Argentinas 435, 1405 Buenos Aires, Argentina
Palabras clave:Adenovector; Akinesia; Cytokine; Inflammation; Microglia; Parkinson; interleukin 1beta; Adenovirus; akinesia; animal experiment; animal model; animal tissue; article; astrocyte; cell activation; cell death; controlled study; disease course; dopaminergic nerve cell; immunohistochemistry; inflammatory infiltrate; male; microglia; motor dysfunction; nerve degeneration; nonhuman; pathogenesis; pathophysiology; priority journal; protein expression; rat; scar formation; substantia nigra; virus recombinant; Adenoviridae; Animals; Astrocytes; Cell Death; Cytokines; Dopamine; Genetic Vectors; Glial Fibrillary Acidic Protein; Interleukin-1; Macrophage Activation; Macrophages; Male; Microglia; Motor Activity; Movement Disorders; Nerve Degeneration; Neuroglia; Neurons; Parkinson Disease, Secondary; Rats; Rats, Wistar; Substantia Nigra
Año:2006
Volumen:24
Número:1
Página de inicio:183
Página de fin:193
DOI: http://dx.doi.org/10.1016/j.nbd.2006.06.013
Título revista:Neurobiology of Disease
Título revista abreviado:Neurobiol. Dis.
ISSN:09699961
CODEN:NUDIE
CAS:Cytokines; Dopamine, 51-61-6; Glial Fibrillary Acidic Protein; Interleukin-1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09699961_v24_n1_p183_Ferrari

Referencias:

  • Allan, S.M., Rothwell, N.J., Cytokines and acute neurodegeneration (2001) Nat. Rev., Neurosci., 2, pp. 734-744
  • Anthony, D.C., Bolton, S.J., Fearn, S., Perry, V.H., Age-related effects of interleukin-1 beta on polymorphonuclear neutrophil-dependent increases in blood-brain barrier permeability in rats (1997) Brain, 120 (PART 3), pp. 435-444
  • Barcia, C., SanchezBahillo, A., Fernandez-Villalba, E., Bautista, V., Poza, Y., Poza, M., Fernandez-Barreiro, A., Herrero, M.T., Evidence of active microglia in substantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure (2004) Glia, 46 (4), pp. 402-409
  • Blond, D., Campbell, S.J., Butchart, A.G., Perry, V.H., Anthony, D.C., Differential induction of interleukin-1beta and tumour necrosis factor-alpha may account for specific patterns of leukocyte recruitment in the brain (2002) Brain Res., 958, pp. 89-99
  • Boutin, H., LeFeuvre, R.A., Horai, R., Asano, M., Iwakura, Y., Rothwell, N.J., Role of IL-1alpha and IL-1beta in ischemic brain damage (2001) J. Neurosci., 21, pp. 5528-5534
  • Carvey, P.M., Chen, E.Y., Lipton, J.W., Tong, C.W., Chang, Q.A., Ling, Z.D., Intra-parenchymal injection of tumor necrosis factor-alpha and interleukin 1-beta produces dopamine neuron loss in the rat (2005) J. Neural Transm., 112, pp. 601-612
  • Castano, A., Herrera, A.J., Cano, J., Machado, A., Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system (1998) J. Neurochem., 70, pp. 1584-1592
  • Castano, A., Herrera, A.J., Cano, J., Machado, A., The degenerative effect of a single intranigral injection of LPS on the dopaminergic system is prevented by dexamethasone, and not mimicked by rh-TNF-alpha IL-1beta and IFN-gamma (2002) J. Neurochem., 81, pp. 150-157
  • Cicchetti, F., Brownell, A.L., Williams, K., Chen, Y.I., Livni, E., Isacson, O., Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging (2002) Eur. J. Neurosci., 15, pp. 991-998
  • Combrinck, M.I., Perry, V.H., Cunningham, C., Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine prion disease (2002) Neuroscience, 112, pp. 7-11
  • Cunningham, C., Wilcockson, D.C., Campion, S., Lunnon, K., Perry, V.H., Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration (2005) J. Neurosci., 25, pp. 9275-9284
  • Depino, A.M., Earl, C., Kaczmarczyk, E., Ferrari, C., Besedovsky, H., del Rey, A., Pitossi, F.J., Oertel, W.H., Microglial activation with atypical proinflammatory cytokine expression in a rat model of Parkinson's disease (2003) Eur. J. Neurosci., 18, pp. 2731-2742
  • Depino, A., Ferrari, C., Pott Godoy, M.C., Tarelli, R., Pitossi, F.J., Differential effects of interleukin-1beta on neurotoxicity, cytokine induction and glial reaction in specific brain regions (2005) J. Neuroimmunol., 168, pp. 96-110
  • Dinarello, CA., Interleukin-1 (1997) Cytokine Growth Factor Rev., 8, pp. 253-265
  • Ferrari, C.C., Depino, A.M., Prada, F., Muraro, N., Campbell, S., Podhajcer, O., Perry, V.H., Pitossi, F.J., Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain (2004) Am. J. Pathol., 165, pp. 1827-1837
  • Forno, L.S., Neuropathologic features of Parkinson's, Huntington's, and Alzheimer's diseases (1992) Ann. N. Y. Acad. Sci., 648, pp. 6-16
  • Gao, H.M., Liu, B., Zhang, W., Hong, J.S., Novel anti-inflammatory therapy for Parkinson's disease (2003) Trends Pharmacol Sci, 24, pp. 395-401
  • Griffin, W.S., Mrak, R.E., Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer's disease (2002) J. Leukocyte Biol.., 72, pp. 233-238
  • Hagan, J.J., Middlemiss, D.N., Sharpe, P.C., Poste, G.H., Parkinson's disease: prospects for improved drug therapy (1997) Trends Pharmacol. Sci., 18, pp. 156-163
  • Hald, A., Lotharius, J., Oxidative stress and inflammation in Parkinson's disease: is there a causal link? (2005) Exp. Neurol., 193, pp. 279-290
  • He, Y., Appel, S., Le, W., Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum (2001) Brain Res., 909, pp. 187-193
  • Hirsch, E.C., Breidert, T., Rousselet, E., Hunot, S., Hartmann, A., Michel, P.P., The role of glial reaction and inflammation in Parkinson's disease (2003) Ann. N. Y. Acad. Sci., 991, pp. 214-228
  • Hirsch, E.C., Hunot, S., Hartmann, A., Neuroinflammatory processes in Parkinson's disease (2005) Parkinsonism Relat. Disord., 11 (SUPPL. 1), pp. S9-S15
  • Huitinga, I., vanderCammen, M., Salm, L., Erkut, Z., van Dam, A., Tilders, F., Swaab, D., IL-1beta immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis (2000) J. Neuroimmunol., 107, pp. 8-20
  • Hunot, S., Dugas, N., Faucheux, B., Hartmann, A., Tardieu, M., Debre, P., Agid, Y., Hirsch, E.C., FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells (1999) J. Neurosci., 19, pp. 3440-3447
  • Hurley, S.D., O'Banion, M.K., Song, D.D., Arana, F.S., Olschowka, J.A., Haber, S.N., Microglial response is poorly correlated with neurodegeneration following chronic, low-dose MPTP administration in monkeys (2003) Exp. Neurol., 184 (2), pp. 659-668
  • Iravani, M.M., Kashefi, K., Mander, P., Rose, S., Jenner, P., Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration (2002) Neuroscience, 110, pp. 49-58
  • Kaur, C., Ling, E.A., Study of the transformation of amoeboid microglial cells into microglia labelled with the isolectin Griffonia simplicifolia in postnatal rats (1991) Acta Anat. (Basel), 142, pp. 118-125
  • Kim, W.G., Mohney, R.P., Wilson, B., Jeohn, G.H., Liu, B., Hong, J.S., Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia (2000) J. Neurosci., 20, pp. 6309-6316
  • Kolb, M., Margetts, P.J., Anthony, D.C., Pitossi, F., Gauldie, J., Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis (2001) J. Clin. Invest., 107, pp. 1529-1536
  • Kreutzberg, G.W., Microglia: a sensor for pathological events in the CNS (1996) Trends Neurosci., 19, pp. 312-318
  • Lang, A.E., Lozano, A.M., Parkinson's disease (1998) Second of two parts: N. Engl. J. Med., 339, pp. 1130-1143
  • Langston, J.W., Forno, L.S., Tetrud, J., Reeves, A.G., Kaplan, J.A., Karluk, D., Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure (1999) Ann. Neurol., 46, pp. 598-605
  • Lawrence, C.B., Allan, S.M., Rothwell, N.J., Interleukin-1beta and the interleukin-1 receptor antagonist act in the striatum to modify excitotoxic brain damage in the rat (1998) Eur. J. Neurosci., 10, pp. 1188-1195
  • Liberatore, G.T., Finkelstein, D.I., Wong, J.Y., Horne, M.K., Porritt, M.J., Donnan, G.A., Howells, D.W., Sprouting of dopaminergic axons after striatal injury: confirmation by markers not dependent on dopamine metabolism (1999) Exp. Neurol., 159, pp. 565-573
  • Liu, B., Du, L., Hong, J.S., Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation (2000) J. Pharmacol. Exp. Ther., 293, pp. 607-617
  • Liu, B., Jiang, J.W., Wilson, B.C., Du, L., Yang, S.N., Wang, J.Y., Wu, G.C., Hong, J.S., Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide (2000) J. Pharmacol. Exp. Ther., 295, pp. 125-132
  • McGeer, P.L., Itagaki, S., Akiyama, H., McGeer, E.G., Rate of cell death in parkinsonism indicates active neuropathological process (1988) Ann. Neurol., 24, pp. 574-576
  • McGeer, P.L., Schwab, C., Parent, A., Doudet, D., Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration (2003) Ann. Neurol. Nov., 54 (5), pp. 599-604
  • Mirza, B., Hadberg, H., Thomsen, P., Moos, T., The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease (2000) Neuroscience, 95, pp. 425-432
  • Mogi, M., Nagatsu, T., Neurotrophins and cytokines in Parkinson's disease (1999) Adv. Neurol., 80, pp. 135-139
  • Mogi, M., Harada, M., Kondo, T., Riederer, P., Inagaki, H., Minami, M., Nagatsu, T., Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients (1994) Neurosci. Lett., 180, pp. 147-150
  • Nagatsu, T., Parkinson's disease: changes in apoptosis-related factors suggesting possible gene therapy (2002) J. Neural Transm., 109, pp. 731-745
  • Orr, C.F., Rowe, D.B., Halliday, G.M., An inflammatory review of Parkinson's disease (2002) Prog. Neurobiol., 68, pp. 325-340
  • Parish, C.L., Finkelstein, D.I., Tripanichkul, W., Satoskar, A.R., Drago, J., Horne, M.K., The role of interleukin-1, interleukin-6, and glia in inducing growth of neuronal terminal arbors in mice (2002) J. Neurosci., 22, pp. 8034-8041
  • Paxinos, G., Watson, C., (1986) The Rat Brain in Stereotaxic Coordinates, , Academic Press, Orlando, FL
  • Pearson, V.L., Rothwell, N.J., Toulmond, S., Excitotoxic brain damage in the rat induces interleukin-1beta protein in microglia and astrocytes: correlation with the progression of cell death (1999) Glia, 25, pp. 311-323
  • Perry, V., Cunningham, C., Boche, D., Atypical inflammation in the central nervous system in prion disease (2002) Current Opin. Neurol., 15, pp. 349-354
  • Perry, V.H., Newman, T.A., Cunningham, C., The impact of systemic infection on the progression of neurodegenerative disease (2003) Nat. Rev., Neurosci., 4, pp. 103-112
  • Przedborski, S., Vila, M., Jackson-Lewis, V.V., Dawson, T.M., Reply: a new look at the pathogenesis of Parkinson's disease (2000) Trends Pharmacol. Sci., 21, p. 165
  • Rodrigues, R.W., Gomide, V.C., Chadi, G., Astroglial and microglial reaction after a partial nigrostriatal degeneration induced by the striatal injection of different doses of 6-hydroxydopamine (2001) Int. J. Neurosci., 109, pp. 91-126
  • Sanchez-Pernaute, R., Ferree, A., Cooper, O., Yu, M., Brownell, A.L., Isacson, O., Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease (2004) J. Neuroinflammation, 1, p. 6
  • Saura, J., Pares, M., Bove, J., Pezzi, S., Alberch, J., Marin, C., Tolosa, E., Marti, M.J., Intranigral infusion of interleukin-1beta activates astrocytes and protects from subsequent 6-hydroxydopamine neurotoxicity (2003) J. Neurochem., 85, pp. 651-661
  • Schallert, T., Jones, T.A., Exuberant neuronal growth after brain damage in adult rats: the essential role of behavioral experience (1993) J. Neural Transplant. Plast., 4, pp. 193-198
  • Sheng, J.G., Shirabe, S., Nishiyama, N., Schwartz, J.P., Alterations in striatal glial fibrillary acidic protein expression in response to 6-hydroxydopamine-induced denervation (1993) Exp. Brain Res., 95, pp. 450-456
  • Sugama, S., Cho, B.P., Degiorgio, L.A., Shimizu, Y., Kim, S.S., Kim, Y.S., Shin, D.H., Joh, T.H., Temporal and sequential analysis of microglia in the substantia nigra following medial forebrain bundle axotomy in rat (2003) Neuroscience, 116, pp. 925-933
  • Teismann, P., Schulz, J.B., Cellular pathology of Parkinson's disease: astrocytes, microglia and inflammation (2004) Cell Tissue Res., 318, pp. 149-161
  • Vila, M., Jackson-Lewis, V., Guegan, C., Wu, D.C., Teismann, P., Choi, D.K., Tieu, K., Przedborski, S., The role of glial cells in Parkinson's disease (2001) Curr. Opin. Neurol., 14, pp. 483-489
  • Winkler, C., Kirik, D., Bjorklund, A., Cell transplantation in Parkinson's disease: how can we make it work? (2005) Trends Neurosci., 28, pp. 86-92
  • Wu, D.C., Jackson-Lewis, V., Vila, M., Tieu, K., Teismann, P., Vadseth, C., Choi, D.K., Przedborski, S., Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease (2002) J. Neurosci., 22, pp. 1763-1771

Citas:

---------- APA ----------
Ferrari, C.C., Pott Godoy, M.C., Tarelli, R., Chertoff, M., Depino, A.M. & Pitossi, F.J. (2006) . Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra. Neurobiology of Disease, 24(1), 183-193.
http://dx.doi.org/10.1016/j.nbd.2006.06.013
---------- CHICAGO ----------
Ferrari, C.C., Pott Godoy, M.C., Tarelli, R., Chertoff, M., Depino, A.M., Pitossi, F.J. "Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra" . Neurobiology of Disease 24, no. 1 (2006) : 183-193.
http://dx.doi.org/10.1016/j.nbd.2006.06.013
---------- MLA ----------
Ferrari, C.C., Pott Godoy, M.C., Tarelli, R., Chertoff, M., Depino, A.M., Pitossi, F.J. "Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra" . Neurobiology of Disease, vol. 24, no. 1, 2006, pp. 183-193.
http://dx.doi.org/10.1016/j.nbd.2006.06.013
---------- VANCOUVER ----------
Ferrari, C.C., Pott Godoy, M.C., Tarelli, R., Chertoff, M., Depino, A.M., Pitossi, F.J. Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1β in the substantia nigra. Neurobiol. Dis. 2006;24(1):183-193.
http://dx.doi.org/10.1016/j.nbd.2006.06.013