Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

During aging the hippocampus experiences structural, molecular, and functional alterations. Protection from age-related disorders is provided by several factors, including estrogens. Since aging defects start at middle age, we studied if 17 β-estradiol (E2) protected the hippocampus at this age period. Middle age (10-12 month old) male C57Bl/6 mice were implanted sc with E2 (15 μg) or cholesterol pellets. Ten days afterwards they received bromodeoxyuridine (BrdU) 4 and 2 h before killing to study cell proliferation in the dentate gyrus (DG). A pronounced depletion of BrdU+cells in the DG was found in cholesterol-treated middle age mice, accompanied by astrocytosis, and by neuronal loss in the hilus. Middle age mice receiving E2 showed increased number of BrdU+cells while the other parameters were remarkably attenuated. When steroid treatment was prolonged for 2 months to study migration of cells in the granular layer of the DG, cell migration was unaffected by E2. However, E2-treated middle age mice presented higher cell density and increased staining for doublecortin, a marker for differentiating neurons. Thus, from the three basic steps of adult neurogenesis (proliferation, migration, and differentiation), E2 stimulated progenitor proliferation-even after long exposure to E2 studied by Ki67 immunocytochemistry-and differentiation towards a neuronal lineage. This result, in conjunction with recovery from other aging indicators as increased deposits of the aging pigment lipofuscin in DG cells, loss of hilar neurons and astrocytosis supports a wide range protection of hippocampal function of middle age mice by estrogenic hormones. © 2007 Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Neuroprotective effects of estradiol in hippocampal neurons and glia of middle age mice
Autor:Saravia, F.; Beauquis, J.; Pietranera, L.; De Nicola, A.F.
Filiación:Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental, 1428 Buenos Aires, Argentina
Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, 1033 Buenos Aires, Argentina
Palabras clave:5-bromo-2′-deoxyuridine (BrdU); Brain aging; Dentate gyrus; doublecortin; Estradiol; Glial fibrillary acidic protein (GFAP); Hilar neurons; Ki67; Lipofuscin; Neurogenesis; Neuroprotection; broxuridine; cholesterol; doublecortin; estradiol; animal cell; animal experiment; animal tissue; article; astrocytosis; cell density; cell differentiation; cell loss; cell migration; cell proliferation; controlled study; dentate gyrus; glia; hippocampus; immunocytochemistry; male; mouse; nerve cell; nervous system development; neuroprotection; nonhuman; priority journal; stem cell; Aging; Animals; Cell Death; Cell Differentiation; Estradiol; Hippocampus; Immunohistochemistry; Male; Mice; Neuroglia; Neurons; Neuroprotective Agents; Sex Factors; Stem Cells
Año:2007
Volumen:32
Número:5
Página de inicio:480
Página de fin:492
DOI: http://dx.doi.org/10.1016/j.psyneuen.2007.02.012
Título revista:Psychoneuroendocrinology
Título revista abreviado:Psychoneuroendocrinology
ISSN:03064530
CODEN:PSYCD
CAS:broxuridine, 59-14-3; cholesterol, 57-88-5; doublecortin, 202938-39-4; estradiol, 50-28-2; Estradiol, 50-28-2; Neuroprotective Agents
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064530_v32_n5_p480_Saravia

Referencias:

  • Anderson, M.F., Aberg, M.A., Nilsson, M., Eriksson, P.S., Insulin-like growth factor-I and neurogenesis in the adult mammalian brain (2002) Dev. Brain Res., 134, pp. 115-122
  • Azcoitia, I., Sierra, A., Garcia-Segura, L.M., Estradiol prevents kainic acid-induced neuronal loss in the rat dentate gyrus (1998) Neuroreport, 9, pp. 3075-3079
  • Azcoitia, I., Sierra, A., Garcia-Segura, L.M., Localization of estrogen receptor beta-immunoreactivity in astrocytes of the adult rat brain (1999) Glia, 26, pp. 260-267
  • Beauquis, J., Roig, P., Homo-Delarche, F., De Nicola, A.F., Saravia, F., Reduced hippocampal neurogenesis and number of hilar neurones in streptozotocin-diabetic mice: reversion by antidepressant treatment (2006) Eur. J. Neurosci., 23, pp. 1539-1546
  • Behl, C., Estrogen as a neuroprotective hormone (2002) Nat. Rev. Neurosci., 3, pp. 433-442
  • Brewer, G.J., Reichensperger, J.D., Brinton, R.D., Prevention of age-related dysregulation of calcium dynamics by estrogen in neurons (2006) Neurobiol. Aging, 27, pp. 306-317
  • 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) J. Comp. Neurol., 467, pp. 1-10
  • Cadacio, C.L., Milner, T.A., Gallagher, M., Pierce, J.P., Hilar neuropeptide Y interneuron loss in the aged rat hippocampal formation (2003) Exp. Neurol., 183, pp. 147-158
  • Cameron, H.A., McKay, R.D., Restoring production of hippocampal neurons in old age (1999) Nat. Neurosci., 2, pp. 894-897
  • Cameron, H.A., Woolley, C.S., McEwen, B.S., Gould, E., Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat (1993) Neuroscience, 56, pp. 337-344
  • Cardona-Gomez, G.P., Mendez, P., DonCarlos, L.L., Azcoitia, I., Garcia-Segura, L.M., Interactions of estrogens and insulin-like growth factor-I in the brain: implications for neuroprotection (2001) Brain Res. Rev., 37, pp. 320-334
  • Coggeshall, R., Lekan, H., Methods for determining numbers of cells and synapses: a case for more uniform standards of review (1996) J. Comp. Neurol., 364, pp. 6-15
  • Dalm, S., Enthoven, L., Meijer, O.C., van der Mark, M.H., Karssen, A.M., de Kloet, E.R., Oitzl, M.S., Age-related changes in hypothalamic-pituitary-adrenal axis activity of male C57BL/6 J mice (2005) Neuroendocrinology, 81, pp. 372-380
  • Darnaudery, M., Perez-Martin, M., Belizaire, G., Maccari, S., Garcia-Segura, L.M., Insulin-like growth factor 1 reduces age-related disorders induced by prenatal stress in female rats (2006) Neurobiol. Aging, 27, pp. 119-127
  • David, J.-P., Fallet-Bianc, C., Vermersch, P., Frigard, B., Di Menza, C., Delacourte, A., Viellissement cerebral normal: étude de la réaction gliale (1994) C R Acad. Sci. Paris, 317, pp. 749-753
  • Day, J.R., Laping, N.J., Lampert-Etchells, M., Brown, S.A., O'Callaghan, J.P., McNeill, T.H., Finch, C.E., Gonadal steroids regulate the expression of glial fibrillary acidic protein in the adult male rat hippocampus (1993) Neuroscience, 55, pp. 435-443
  • Diaz-Brinton, R., Chen, S., Montoya, M., Hsieh, D., Minaya, J., Kim, J., Chu, H.P., The women's health initiative estrogen replacement therapy is neurotrophic and neuroprotective (2000) Neurobiol. Aging, 21, pp. 475-496
  • Driscoll, I., Sutherland, R.J., The aging hippocampus: navigating between rat and human experiments (2005) Rev. Neurosci., 16, pp. 87-121
  • 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, pp. 129-137
  • Foster, T.C., Interaction of rapid signal transduction cascades and gene expression in mediating estrogen effects on memory over the life span (2005) Front Neuroendocrinol., 26, pp. 51-64
  • Galea, L.A., Spritzer, M.D., Barker, J.M., Pawluski, J.L., Gonadal hormone modulation of hippocampal neurogenesis in the adult (2006) Hippocampus, 16, pp. 225-232
  • Garcia-Ovejero, D., Veiga, S., Garcia-Segura, L.M., Doncarlos, L.L., Glial expression of estrogen and androgen receptors after rat brain injury (2002) J. Comp. Neurol., 450, pp. 256-271
  • García-Segura, L.M., Azcoitia, I., DonCarlos, L.L., Neuroprotection by estradiol (2001) Prog. Neurobiol., 63, pp. 29-60
  • Goss, J.R., Finch, C.E., Morgan, D.G., Age-related changes in glial fibrillary acidic protein mRNA in the mouse brain (1991) Neurobiol. Aging, 12, pp. 165-170
  • Gould, E., Tanapat, P., Rydel, T., Hastings, N., Regulation of hippocampal neurogenesis in adulthood (2000) Biol. Psychiatry, 48, pp. 715-720
  • Gundersen, H.J.G., Jensen, E.B., The efficacy of systematic sampling in stereology and its prediction (1987) J. Microsc., 147, pp. 229-263
  • Hastings, N.B., Gould, E., Rapid extension of axons into the CA3 region by adult-generated granule cells (1999) J. Comp. Neurol., 413, pp. 146-154
  • He, J., Nixon, K., Shetty, A.K., Crews, F.T., Chronic alcohol exposure reduces hippocampal neurogenesis and dendritic growth of newborns neurons (2005) Eur. J. Neurosci., 21, pp. 2711-2720
  • Heine, V.M., Maslam, S., Joels, M., Lucassen, P.J., Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation (2004) Neurobiol. Aging, 25, pp. 361-375
  • Henderson, V.W., Paganini-Hill, A., Emanuel, C.K., Dunn, M.E., Buckwalter, J.G., Estrogen replacement therapy in older women. Comparisons between Alzheimer's disease cases and nondemented control subjects (1994) Arch. Neurol., 51, pp. 896-900
  • Howard, C.V., Reed, M.G., (1998) Unbiased Stereology. Three-Dimensional Measurement in Microscopy, , BIOS Scientific Publishers, Oxford
  • Isgor, C., Cecchi, M., Kabbai, M., Akil, H., Watson, S.J., Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates the neuroendocrine response to stress and is regulated by corticosterone (2003) Neuroscience, 121, pp. 837-845
  • Kempermann, G., Gast, D., Gage, F.H., Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment (2002) Ann Neurol., 52, pp. 135-143
  • Keller, J.N., Dimayuga, E., Chen, Q., Thorpe, J., Gee, J., Ding, Q., Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain (2004) Int. J. Biochem. Cell Biol., 36, pp. 2376-2391
  • Kuhn, H.G., Dickinson-Anson, H., Gage, F.H., Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation (1996) J. Neurosci., 16, pp. 2027-2033
  • Larsson, A., Wilhelmsson, U., Pekna, M., Pekny, M., Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(-/-)Vim(-/-) mice (2004) Neurochem. Res., 29, pp. 2069-2073
  • Lei, D.L., Long, J.M., Hengemihle, J., O'Neill, J., Manaye, K.F., Ingram, D.K., Mouton, P.R., Effects of estrogen and raloxifene on neuroglia number and morphology in the hippocampus of aged female mice (2003) Neuroscience, 121, pp. 659-666
  • Magariňos, A.M., McEwen, B.S., Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress (2000) Proc. Natl. Acad. Sci. USA, 97, pp. 11056-11061
  • McDonald, H.Y., Wojtowicz, J.M., Dynamics of neurogenesis in the dentate gyrus of adult rats (2005) Neurosci. Lett., 385, pp. 70-75
  • McEwen, B.S., Stress and the aging hippocampus (1999) Front Neuroendocrinol., 20, pp. 40-79
  • McEwen, B.S., Akama, K., Alves, S., Brake, S.G., Bulloch, K., Lee, S., Li, C., Milner, T.A., Tracking the estrogen receptor in neurons: implications for estrogen-induced synapse formation (2001) Proc. Natl. Acad. Sci. USA, 98, pp. 7093-7100
  • Miller, D.B., O'Callaghan, J.P., Aging, stress and the hippocampus (2005) Ageing Res. Rev., 4, pp. 123-140
  • Mody, I., Otis, T.S., Bragin, A., Hsu, M., Bizsaki, G., GABAergic inhibition of granule cells and hilar al synchrony following ischemia-induced hilar neuronal loss (1995) Neuroscience, 69, pp. 139-150
  • Moorthy, K., Yadav, U.C., Siddiqui, M.R., Mantha, A.K., Basir, S.F., Sharma, D., Cowsik, S.M., Baquer, N.Z., Effect of hormone replacement therapy in normalizing age related neuronal markers in different age groups of naturally menopausal rats (2005) Biogerontology, 6, pp. 345-356
  • Nichols, N.R., Day, J.R., Laping, N.J., Johnson, S.A., Finch, C.E., GFAP mRNA increases with age in rat and human brain (1993) Neurobiol. Aging, 14, pp. 421-429
  • Ormerod, B.K., Lee, T.T.-L., Galea, L.A.M., Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats (2003) J. Neurobiol., 55, pp. 247-260
  • Pekny, M., Nilsson, M., Astrocyte activation and reactive gliosis (2005) Glia, 50, pp. 427-434
  • Perez-Martin, M., Salazar, V., Castillo, C., Ariznavarreta, C., Azcoitia, I., Garcia-Segura, L.M., Tresguerres, J.A., Estradiol and soy extract increase the production of new cells in the dentate gyrus of old rats (2005) Exp. Gerontol., 40, pp. 450-453
  • Picazo, O., Azcoitia, I., Garcia-Segura, L.M., Neuroprotective and neurotoxic effects of estrogens (2003) Brain Res., 990, pp. 20-27
  • Resnick, S.M., Maki, P.M., Rapp, S.R., Espeland, M.A., Brunner, R., Coker, L.H., Granek, I.A., Shumaker, S.A., Women's health initiative study of cognitive aging investigators. Effects of combination estrogen plus progestin hormone treatment on cognition and affect (2006) J. Clin. Endocrinol. Metab., 9, pp. 1802-1810
  • Rivas-Arancibia, S., Dorado-Martinez, C., Colin-Barenque, L., Kendrick, K.M., de la Riva, C., Guevara-Guzman, R., Effect of acute ozone exposure on locomotor behavior and striatal function (2003) Pharmacol. Biochem. Behav., 74, pp. 891-900
  • Rozovsky, I., Wei, M., Stone, D.J., Zanjani, H., Anderson, C.P., Morgan, T.E., Finch, C.E., Estradiol (E2) enhances neurite outgrowth by repressing glial fibrillary acidic protein expression and reorganizing laminin (2002) Endocrinology, 143, pp. 636-646
  • Sapolsky, R.M., Glucocorticoids, stress and their adverse neurological effects: relevance to aging (1999) Exp. Gerontol., 34, pp. 721-723
  • Saravia, F., Revsin, Y., Lux-Lantos, V., Beauquis, J., Homo-Delarche, F., De Incola, A.F., Oestradiol restores cell proliferation in dentate gyrus and subventricular zone of streptozotocin-diabetic rats (2004) J. Neuroendocrinol., 16, pp. 704-710
  • Saravia, F., Beauquis, J., Revsin, Y., Homo-Delarche, F., de Kloet, E.R., De Nicola, A.F., Hippocampal neuropathology of diabetes mellitus is relieved by estrogen treatment (2006) Cell Mol. Neurobiol., 26, pp. 943-957
  • Scharfman, H.E., Maclusky, N.J., Similarities between actions of estrogen and BDNF in the hippocampus: coincidence or clue? (2005) Trends Neurosci., 28, pp. 79-85
  • Smith, R.G., Betancourt, L., Sun, Y., Molecular endocrinology and physiology of the aging central nervous system (2005) Endocrinol. Rev., 26, pp. 203-250
  • Shors, T.J., Townsend, D.A., Zhao, M., Kozorovitskiy, Y., Gould, E., Neurogenesis may relate to some but not all types of hippocampal-dependent learning (2002) Hippocampus, 12, pp. 578-584
  • Shughrue, P.J., Merchenthaler, I., Evidence for novel estrogen binding sites in the rat hippocampus (2000) Neuroscience, 99, pp. 605-612
  • Stone, D.J., Song, Y., Anderson, C.P., Krohn, K.K., Finch, C.E., Rozovsky, I., Bidirectional transcription regulation of glial fibrillary acidic protein by estradiol in vivo and in vitro (1998) Endocrinology, 139, pp. 3202-3209
  • Tanapat, P., Hastings, N.B., Reeves, A.J., Gould, E., Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat (1999) J. Neurosci., 19, pp. 5792-5801
  • Tanapat, P., Hastings, N.B., Gould, E., Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose- and time-dependent manner (2005) J. Comp. Neurol., 481, pp. 252-265
  • Van Eekelen, J.A.M., Rots, N.Y., Sutanto, W., de Kloet, E.R., The effect of aging on stress responsiveness and central corticosteroid receptors in the Brown Norway rat (1991) Neurobiol. Aging, 13, pp. 159-170
  • Wang, P.N., Liao, S.Q., Liu, R.S., Liu, C.Y., Chao, H.T., Lu, S.R., Yu, H.Y., Liu, H.C., Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study (2000) Neurology, 54, pp. 2061-2066
  • West, M., Regionally specific loss of neurons in the aging human hippocampus (1993) Neurobiol. Aging, 14, pp. 287-293
  • Wise, P.M., Estrogen therapy: does it help or hurt the adult and aging brain? Insights derived from animal models (2006) Neuroscience, 138, pp. 831-835
  • Wong, E.Y.H., Herbert, J., Roles of mineralocorticoid and glucocorticoid receptors in the regulation of progenitor proliferation in the adult hippocampus (2005) Eur. J. Neurosci., 22, pp. 785-792

Citas:

---------- APA ----------
Saravia, F., Beauquis, J., Pietranera, L. & De Nicola, A.F. (2007) . Neuroprotective effects of estradiol in hippocampal neurons and glia of middle age mice. Psychoneuroendocrinology, 32(5), 480-492.
http://dx.doi.org/10.1016/j.psyneuen.2007.02.012
---------- CHICAGO ----------
Saravia, F., Beauquis, J., Pietranera, L., De Nicola, A.F. "Neuroprotective effects of estradiol in hippocampal neurons and glia of middle age mice" . Psychoneuroendocrinology 32, no. 5 (2007) : 480-492.
http://dx.doi.org/10.1016/j.psyneuen.2007.02.012
---------- MLA ----------
Saravia, F., Beauquis, J., Pietranera, L., De Nicola, A.F. "Neuroprotective effects of estradiol in hippocampal neurons and glia of middle age mice" . Psychoneuroendocrinology, vol. 32, no. 5, 2007, pp. 480-492.
http://dx.doi.org/10.1016/j.psyneuen.2007.02.012
---------- VANCOUVER ----------
Saravia, F., Beauquis, J., Pietranera, L., De Nicola, A.F. Neuroprotective effects of estradiol in hippocampal neurons and glia of middle age mice. Psychoneuroendocrinology. 2007;32(5):480-492.
http://dx.doi.org/10.1016/j.psyneuen.2007.02.012