The selective glucocorticoid receptor modulator CORT108297 restores faulty hippocampal parameters in Wobbler and corticosterone-treated mice
Mutant Wobbler mice are models for human amyotrophic lateral sclerosis (ALS). In addition to spinal cord degeneration, Wobbler mice show high levels of blood corticosterone, hyperactivity of the hypothalamic-pituitary-adrenal axis and abnormalities of the hippocampus. Hypersecretion of glucocorticoi...
Guardado en:
| Autor principal: | |
|---|---|
| Otros Autores: | , , , |
| Formato: | Capítulo de libro |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier Ltd
2014
|
| Materias: | |
| Acceso en línea: | Registro en Scopus DOI Handle Registro en la Biblioteca Digital |
| Aporte de: | Registro referencial: Solicitar el recurso aquí |
| Sumario: | Mutant Wobbler mice are models for human amyotrophic lateral sclerosis (ALS). In addition to spinal cord degeneration, Wobbler mice show high levels of blood corticosterone, hyperactivity of the hypothalamic-pituitary-adrenal axis and abnormalities of the hippocampus. Hypersecretion of glucocorticoids increase hippocampus vulnerability, a process linked to an enriched content of glucocorticoid receptors (GR). Hence, we studied if a selective GR antagonist (CORT108297) with null affinity for other steroid receptors restored faulty hippocampus parameters of Wobbler mice. Three months old genotyped Wobbler mice received s.c. vehicle or CORT108297 during 4 days. We compared the response of doublecortin (DCX)+ neuroblasts in the subgranular layer of the dentate gyrus (DG), NeuN+ cells in the hilus of the DG, glial fibrillary acidic protein (GFAP)+ astrocytes and the phenotype of Iba1+ microglia in CORT108297-treated and vehicle-treated Wobblers. The number of DCX+ cells in Wobblers was lower than in control mice, whereas CORT108297 restored this parameter. After CORT108297 treatment, Wobblers showed diminished astrogliosis, and changed the phenotype of Iba1+ microglia from an activated to a quiescent form. These changes occurred without alterations in the hypercorticosteronemia or the number of NeuN+ cells of the Wobblers. In a separate experiment employing control NFR/NFR mice, treatment with corticosterone for 5 days reduced DCX+ neuroblasts and induced astrocyte hypertrophy, whereas treatment with CORT108297 antagonized these effects. Normalization of neuronal progenitors, astrogliosis and microglial phenotype by CORT108297 indicates the usefulness of this antagonist to normalize hippocampus parameters of Wobbler mice. Thus, CORT108297 opens new therapeutic options for the brain abnormalities of ALS patients and hyperadrenocorticisms. © 2014 Elsevier Ltd. |
|---|---|
| Bibliografía: | Gordon, P.H., Amyotrophic Lateral Sclerosis: An update for 2013 clinical features, pathophysiology, management and therapeutic trials (2013) Aging Dis., 4, pp. 295-310 Brettschneider, J., Del Tredici, K., Toledo, J.B., Robinson, J.L., Irwin, D.J., Grossman, M., Suh, E., Trojanowski, J.Q., Stages of pTDP-43 pathology in amyotrophic lateral sclerosis (2013) Ann. Neurol., 74, pp. 20-38 Takeda, T., Uchihara, T., Arai, N., Mizutani, T., Iwata, M., Progression of hippocampal degeneration in amyotrophic lateral sclerosis with or without memory impairment: Distinction from Alzheimer disease (2009) Acta Neuropathol., 117, pp. 35-44 Yokota, O., Terada, S., Ishizu, H., Ishihara, T., Nakashima, H., Kugo, A., Tsuchiya, K., Kuroda, S., Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia (2004) Acta Neuropathologica, 107 (5), pp. 399-405. , DOI 10.1007/s00401-004-0826-2 Schmitt-John, T., Drepper, C., Mussmann, A., Hahn, P., Kuhlmann, M., Thiel, C., Hafner, M., Jockusch, H., Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse (2005) Nature Genetics, 37 (11), pp. 1213-1215. , DOI 10.1038/ng1661, PII N1661 Meyer, M., Gonzalez Deniselle, M.C., Gargiulo-Monachelli, G., Lima, A., Roig, P., Guennoun, R., Schumacher, M., De Nicola, A.F., Progesterone attenuates several hippocampal abnormalities of the Wobbler mouse (2013) J. Neuroendocrinol., 25, pp. 235-243 Patacchioli, F.R., Monnazzi, P., Scontrini, A., Tremante, E., Caridi, I., Brunetti, E., Buttarelli, F.R., Pontieri, F.E., Adrenal dysregulation in amyotrophic lateral sclerosis (2003) J. Endocrinol. Invest., 26, pp. 23-RC25 Gargiulo Monachelli, G., Meyer, M., Rodriguez, G.E., Garay, L.I., Sica, R.E., De Nicola, A.F., Gonzalez Deniselle, M.C., Endogenous progesterone is associated to amyotrophic lateral sclerosis prognostic factors (2011) Acta Neurol. Scand., 123, pp. 60-67 Roozendaal, B., Kim, S., Wolf, O.T., Kim, M.S., Sung, K.K., Lee, S., The cortisol awakening response in amyotrophic lateral sclerosis is blunted and correlates with clinical status and depressive mood (2012) Psychoneuroendocrinology, 37, pp. 20-26 Fidler, J.A., Treleaven, C.M., Frakes, A., Tamsett, T.J., McCrate, M., Cheng, S.H., Shihabuddin, L.S., Dodge, J.C., Disease progression in a mouse model of amyotrophic lateral sclerosis: The influence of chronic stress and corticosterone (2011) FASEB J., 25, pp. 4369-4377 Gonzalez Deniselle, M.C., Gonzalez, S., Piroli, G., Ferrini, M., Lima, A.E., De Nicola, A.F., Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse a model for neurodegenerative diseases (1997) Journal of Steroid Biochemistry and Molecular Biology, 60 (3-4), pp. 205-213. , DOI 10.1016/S0960-0760(96)00193-8, PII S0960076096001938 Green, K.N., Billings, L.M., Roozendaal, B., McGaugh, J.L., LaFerla, F.M., Glucocorticoids increase amyloid-β and tau pathology in a mouse model of Alzheimer's disease (2006) Journal of Neuroscience, 26 (35), pp. 9047-9056. , http://www.jneurosci.org/cgi/reprint/26/35/9047.pdf, DOI 10.1523/JNEUROSCI.2797-06.2006 Revsin, Y., Rekers, N.V., Louwe, M.C., Saravia, F.E., De Nicola, A.F., De Kloet, E.R., Oitzl, M.S., Glucocorticoid receptor blockade normalizes hippocampal alterations and cognitive impairment in streptozotocin-induced type 1 diabetes mice (2009) Neuropsychopharmacology, 34, pp. 747-758 Yi, S.S., Hwang, I.K., Shin, J.H., Choi, J.H., Lee, C.H., Kim, I.Y., Kim, Y.N., Yoon, Y.S., Regulatory mechanism of hypothalamo-pituitary-adrenal (HPA) axis and neuronal changes after adrenalectomy in type 2 diabetes (2010) J. Chem. Neuroanat., 40, pp. 130-139 Bigini, P., Repici, M., Cantarella, G., Fumagalli, E., Barbera, S., Cagnotto, A., De Luigi, A., Mennini, T., Recombinant human TNF-binding protein-1 (rhTBP-1) treatment delays both symptoms progression and motor neuron loss in the wobbler mouse (2008) Neurobiol. Dis., 29, pp. 465-476 Boillee, S., Viala, L., Peschanski, M., Dreyfus, P.A., Differential microglial response to progressive neurodegeneration in the murine mutant wobbler (2001) GLIA, 33 (4), pp. 277-287. , DOI 10.1002/1098-1136(20010315)33:4<277::AID-GLIA1026>3.0.CO;2-Y De Paola, M., Mariani, A., Bigini, P., Peviani, M., Ferrara, G., Molteni, M., Gemma, S., Fanelli, R., Neuroprotective effects of toll-like receptor 4 antagonism in spinal cord cultures and in a mouse model of motor neuron degeneration (2012) Mol. Med., 18, pp. 971-981 Rathke-Hartlieb, S., Schmidt, V.C., Jockusch, H., Schmitt-John, T., Bartsch, J.W., Spatiotemporal progression of neurodegeneration and glia activation in the wobbler neuropathy of the mouse (1999) Neuroreport, 10, pp. 3411-3416 Schlomann, U., Rathke-Hartlieb, S., Yamamoto, S., Jockusch, H., Bartsch, J.W., Tumor necrosis factor alpha induces a metalloprotease-disintegrin, ADAM8 (CD 156): Implications for neuron-glia interactions during neurodegeneration (2000) J. Neurosci., 20, pp. 7964-7971 Anacker, C., Cattaneo, A., Luoni, A., Musaelyan, K., Zunszain, P.A., Milanesi, E., Rybka, J., Pariante, C.M., Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis (2013) Neuropsychopharmacology, 38, pp. 872-883 Cameron, H.A., Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus (1994) Neuroscience, 61 (2), pp. 203-209. , DOI 10.1016/0306-4522(94)90224-0 Ekdahl, C.T., Microglial activation - Tuning and pruning adult neurogenesis (2012) Front Pharmacol., 3, p. 41 Gould, E., The effects of adrenal steroids and excitatory input on neuronal birth and survival (1994) Ann. N.Y. Acad. Sci., 743, pp. 73-92 Monje, M.L., Toda, H., Palmer, T.D., Inflammatory Blockade Restores Adult Hippocampal Neurogenesis (2003) Science, 302 (5651), pp. 1760-1765. , DOI 10.1126/science.1088417 Voloboueva, L.A., Giffard, R.G., Inflammation, mitochondria, and the inhibition of adult neurogenesis (2011) J. Neurosci. Res., 89, pp. 1989-1996 Llorens-Martin, M., Trejo, J.L., Mifepristone prevents stress-induced apoptosis in newborn neurons and increases AMPA receptor expression in the dentate gyrus of C57/BL6 mice (2011) PLoS One, 6, p. 28376 Oomen, C.A., Mayer, J.L., De Kloet, E.R., Joels, M., Lucassen, P.J., Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress (2007) European Journal of Neuroscience, 26 (12), pp. 3395-3401. , DOI 10.1111/j.1460-9568.2007.05972.x Clark, R.D., Ray, N.C., Williams, K., Blaney, P., Ward, S., Crackett, P.H., Hurley, C., Belanoff, J., 1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as selective glucocorticoid receptor antagonists with high functional activity (2008) Bioorganic and Medicinal Chemistry Letters, 18 (4), pp. 1312-1317. , DOI 10.1016/j.bmcl.2008.01.027, PII S0960894X08000413 Brown, J.P., Couillard-Despres, S., Cooper-Kuhn, C.M., Winkler, J., Aigner, L., Kuhn, H.G., Transient Expression of Doublecortin during Adult Neurogenesis (2003) Journal of Comparative Neurology, 467 (1), pp. 1-10. , DOI 10.1002/cne.10874 Pietranera, L., Lima, A., Roig, P., De Nicola, A.F., Involvement of brain-derived neurotrophic factor and neurogenesis in oestradiol neuroprotection of the hippocampus of hypertensive rats (2010) J. Neuroendocrinol., 22, pp. 1082-1092 Keith, B.J.F., George, P., (1997) The Mouse Brain in Stereotaxic Coordinates, , Academic Press Beauquis, J., Roig, P., De Nicola, A.F., Saravia, F., Short-term environmental enrichment enhances adult neurogenesis, vascular network and dendritic complexity in the hippocampus of type 1 diabetic mice (2010) PLoS One, 5, p. 13993 Ciriza, I., Carrero, P., Frye, C.A., Garcia-Segura, L.M., Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective (2006) Journal of Neurobiology, 66 (9), pp. 916-928. , DOI 10.1002/neu.20293 Kreutzberg, G.W., Microglia, the first line of defence in brain pathologies (1995) Arzneimittelforschung., 45, pp. 357-360 Cymeryng, C.B., Dada, L.A., Podesta, E.J., Effect of nitric oxide on rat adrenal zona fasciculata steroidogenesis (1998) Journal of Endocrinology, 158 (2), pp. 197-203. , DOI 10.1677/joe.0.1580197 Gonzalez Deniselle, M.C., Lopez-Costa, J.J., Saavedra, J.P., Pietranera, L., Gonzalez, S.L., Garay, L., Guennoun, R., De Nicola, A.F., Progesterone neuroprotection in the Wobbler mouse, a genetic model of spinal cord motor neuron disease (2002) Neurobiology of Disease, 11 (3), pp. 457-468. , DOI 10.1006/nbdi.2002.0564 De Kloet, E.R., Karst, H., Joels, M., Corticosteroid hormones in the central stress response: Quick-and-slow (2008) Front. Neuroendocrinol., 29, pp. 268-272 Sapolsky, R.M., Krey, L.C., McEwen, B.S., The neuroendocrinology of stress and aging: The glucocorticoid cascade hypothesis (1986) Endocr. Rev., 7, pp. 284-301 Baglietto-Vargas, D., Medeiros, R., Martinez-Coria, H., Laferla, F.M., Green, K.N., Mifepristone alters amyloid precursor protein processing to preclude amyloid beta and also reduces tau pathology (2013) Biol. Psychiatry, 74, pp. 357-366 Zhang, Z., Yang, R., Zhou, R., Li, L., Sokabe, M., Chen, L., Progesterone promotes the survival of newborn neurons in the dentate gyrus of adult male mice (2010) Hippocampus, 20, pp. 402-412 Zalachoras, I., Houtman, R., Atucha, E., Devos, R., Tijssen, A.M., Hu, P., Lockey, P.M., Meijer, O.C., Differential targeting of brain stress circuits with a selective glucocorticoid receptor modulator (2013) PNAS, 110, pp. 7910-7915 Ferrini, M., Piroli, G., Frontera, M., Falbo, A., Lima, A., De Nicola, A.F., Estrogens normalize the hypothalamic-pituitary-adrenal axis response to stress and increase glucocorticoid receptor immunoreactivity in hippocampus of aging male rats (1999) Neuroendocrinology, 69 (2), pp. 129-137. , DOI 10.1159/000054411 Hinterberger, M., Zehetmayer, S., Jungwirth, S., Huber, K., Krugluger, W., Leitha, T., Krampla, W., Fischer, P., High cortisol and low folate are the only routine blood tests predicting probable Alzheimer's disease after age 75-results of the Vienna Transdanube Aging Study (2013) J. Am. Geriatr. Soc., 61, pp. 648-651 Magarinos, A.M., McEwen, B.S., Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress (2000) PNAS, 97, pp. 11056-11061 Hantaz-Ambroise, D., Jacque, C., Ikhlef, A.A., Parmentier, C., Leclerc, P., Cambier, D., Zadigue, G., Rieger, F., Specific features of chronic astrocyte gliosis after experimental Central Nervous System (CNS) xenografting and in Wobbler neurological mutant CNS (2001) Differentiation, 69 (2-3), pp. 100-107 Laage, S., Zobel, G., Jockusch, H., Astrocyte overgrowth in the brain stem and spinal cord of mice affected by spinal atrophy, wobbler (1988) Dev. Neurosci., 10, pp. 190-198 Barbeito, L.H., Pehar, M., Cassina, P., Vargas, M.R., Peluffo, H., Viera, L., Estevez, A.G., Beckman, J.S., A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis (2004) Brain Research Reviews, 47 (1-3), pp. 263-274. , DOI 10.1016/j.brainresrev.2004.05.003, PII S0165017304000700, Chemical and Electrical Synapses Sica, R.E., Is amyotrophic lateral sclerosis a primary astrocytic disease? (2012) Med. Hypotheses, 79, pp. 819-822 González Deniselle, M.C., Lavista-Llanos, S., Ferrini, M.G., Lima, A.E., Roldan, A.G., De Nicola, A.F., In vitro differences between astrocytes of control and wobbler mice spinal cord (1999) Neurochem. Res., 24, pp. 1535-1541 Meyer, M., Gonzalez Deniselle, M.C., Garay, L.I., Monachelli, G.G., Lima, A., Roig, P., Guennoun, R., De Nicola, A.F., Stage dependent effects of progesterone on motoneurons and glial cells of wobbler mouse spinal cord degeneration (2010) Cell Mol. Neurobiol., 30, pp. 123-135 Julien, J.P., ALS: Astrocytes move in as deadly neighbors (2007) Nat. Neurosci., 10, pp. 535-537 Wilhelmsson, U., Faiz, M., De Pablo, Y., Sjoqvist, M., Andersson, D., Widestrand, A., Potokar, M., Pekny, M., Astrocytes negatively regulate neurogenesis through the Jagged1-mediated Notch pathway (2012) Stem Cells, 30, pp. 2320-2329 Bridges, N., Slais, K., Sykova, E., The effects of chronic corticosterone on hippocampal astrocyte numbers: A comparison of male and female Wistar rats (2008) Acta Neurobiologiae Experimentalis, 68 (2), pp. 131-138. , http://www.nencki.gov.pl/pdf/an/vol68/bridges.pdf O'Callaghan, J.P., Brinton, R.E., McEwen, B.S., Glucocorticoids regulate the synthesis of glial fibrillary acidic protein in intact and adrenalectomized rats but do not affect its expression following brain injury (1991) J. Neurochem., 57, pp. 860-869 Claessens, S.E., Belanoff, J.K., Kanatsou, S., Lucassen, P.J., Champagne, D.L., De Kloet, E.R., Acute effects of neonatal dexamethasone treatment on proliferation and astrocyte immunoreactivity in hippocampus and corpus callosum: Towards a rescue strategy (2012) Brain Res., 1482, pp. 1-12 Allaman, I., Pellerin, L., Magistretti, P.J., Glucocorticoids modulate neurotransmitter-induced glycogen metabolism in cultured cortical astrocytes (2004) Journal of Neurochemistry, 88 (4), pp. 900-908 Crossin, K.L., Tai, M.-H., Krushel, L.A., Mauro, V.P., Edelman, G.M., Glucocorticoid receptor pathways are involved in the inhibition of astrocyte proliferation (1997) Proceedings of the National Academy of Sciences of the United States of America, 94 (6), pp. 2687-2692. , DOI 10.1073/pnas.94.6.2687 Yu, S., Yang, S., Holsboer, F., Sousa, N., Almeida, O.F., Glucocorticoid regulation of astrocytic fate and function (2011) PLoS One, 6, p. 22419 Carrillo-De Sauvage, M.A., Maatouk, L., Arnoux, I., Pasco, M., Sanz Diez, A., Delahaye, M., Herrero, M.T., Vyas, S., Potent and multiple regulatory actions of microglial glucocorticoid receptors during CNS inflammation (2013) Cell Death Differ., 20, pp. 1546-1557 Munhoz, C.D., Sorrells, S.F., Caso, J.R., Scavone, C., Sapolsky, R.M., Glucocorticoids exacerbate lipopolysaccharide-induced signaling in the frontal cortex and hippocampus in a dose-dependent manner (2010) J. Neurosci., 30, pp. 13690-13698 Busillo, J.M., Cidlowski, J.A., The five Rs of glucocorticoid action during inflammation: Ready, reinforce, repress, resolve, and restore (2013) Trends Endocrinol. Metab., 24, pp. 109-119 Harpaz, I., Abutbul, S., Nemirovsky, A., Gal, R., Cohen, H., Monsonego, A., Chronic exposure to stress predisposes to higher autoimmune susceptibility in C57BL/6 mice: Glucocorticoids as a double-edged sword (2013) Eur. J. Immunol., 43, pp. 758-769 Frank, M.G., Thompson, B.M., Watkins, L.R., Maier, S.F., Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses (2012) Brain Behav. Immun., 26, pp. 337-345 Lannan, E.A., Galliher-Beckley, A.J., Scoltock, A.B., Cidlowski, J.A., Proinflammatory actions of glucocorticoids: Glucocorticoids and TNFα coregulate gene expression in vitro and in vivo (2012) Endocrinology, 153, pp. 3701-3712 Busillo, J.M., Azzam, K.M., Cidlowski, J.A., Glucocorticoids sensitize the innate immune system through regulation of the NLRP3 inflammasome (2011) J. Biol. Chem., 286, pp. 38703-38713 |
| ISSN: | 09600760 |
| DOI: | 10.1016/j.jsbmb.2014.02.007 |