Artículo

El editor solo permite decargar el artículo en su versión post-print desde el repositorio. Por favor, si usted posee dicha versión, enviela a
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

There is high incidence of hippocampal abnormalities in spontaneously hypertensive rats (SHR), including decreased neurogenesis in the dentate gyrus, astrogliosis, low expression of brain derived neurotrophic factor and decreased neuronal density in the hilar region, respect of normotensive Wistar Kyoto rats (WKY). Estradiol treatment given for 2 weeks normalized the faulty hippocampal parameters of SHR, without having effects on WKY rats. The present work studied the potential role of local estrogen biosynthesis in the hippocampus of SHR and WKY, by measuring the expression of aromatase, the key enzyme responsible for estrogen biosynthesis and involved in neuroprotection. We used 4 month old male SHR and WKY, half of which received a single sc pellet of 12 mg estradiol benzoate and the remaining half a cholesterol implant. Hippocampi were dissected and processed for aromatase mRNA expression using real time PCR. A second batch of animals was processed for aromatase and glial fibrillary acidic protein (GFAP) immunocytochemistry. Basal level of aromatase mRNA was higher in SHR respect of WKY. Following estradiol treatment, aromatase mRNA was further increased in the SHR group only. In the hilus of the dentate gyrus of cholesterol-implanted SHR, we found aromatase immunoreactive cell processes and fibers more strongly stained respect of WKY rats. Estradiol treatment of SHR further increased the length of immunoreactive processes and fibers in the hilar region and also increased aromatase immunoreactivity in the CA1 but not the CA3 pyramidal cell region. WKY rats were spared from the estradiol effect. Double-labelling experiments showed that aromatase+ processes and fibers of the hilus of SHR-treated rats did no colocalize with GFAP+ astrocyte cell bodies or processes. In conclusion, basal and estradiol-stimulated aromatase expression was enhanced in hypertensive rat hippocampus. A combination of exogenous estrogens and those locally synthesized may better alleviate hypertensive encephalopathy. © 2011 IBRO.

Registro:

Documento: Artículo
Título:Increased aromatase expression in the hippocampus of spontaneously hypertensive rats: Effects of estradiol administration
Autor:Pietranera, L.; Bellini, M.J.; Arévalo, M.A.; Goya, R.; Brocca, M.E.; Garcia-Segura, L.M.; De Nicola, A.F.
Filiación:Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Obligado 2490, 1428 Buenos Aires, Argentina
Department of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Paraguay 2155, 1425 Buenos Aires, Argentina
INIBIOLP-Histology B, School of Medicine, Faculty of Medicine, University of La Plata, CC 455, 1900 La Plata, Argentina
Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Avenida Doctor Arce 37, E-28002 Madrid, Spain
Palabras clave:Aromatase; Estradiol; Hippocampus; Neuroprotection; Spontaneously hypertensive rats; aromatase; cholesterol; estradiol benzoate; glial fibrillary acidic protein; messenger RNA; animal cell; animal experiment; animal model; animal tissue; article; astrocyte; controlled study; dentate gyrus; drug mechanism; enzyme activity; estrogen synthesis; hippocampus; immunocompetent cell; immunohistochemistry; immunoreactivity; male; neuroprotection; nonhuman; priority journal; protein expression; protein localization; pyramidal nerve cell; rat; real time polymerase chain reaction; single drug dose; spontaneously hypertensive rat; Animals; Aromatase; Estradiol; Estrogens; Glial Fibrillary Acidic Protein; Hippocampus; Immunohistochemistry; Male; Nerve Fibers; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Species Specificity
Año:2011
Volumen:174
Página de inicio:151
Página de fin:159
DOI: http://dx.doi.org/10.1016/j.neuroscience.2010.11.044
Título revista:Neuroscience
Título revista abreviado:Neuroscience
ISSN:03064522
CODEN:NRSCD
CAS:aromatase, 9039-48-9; cholesterol, 57-88-5; estradiol benzoate, 50-50-0; Aromatase, 1.14.14.1; Estradiol, 50-28-2; Estrogens; Glial Fibrillary Acidic Protein; RNA, Messenger
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v174_n_p151_Pietranera

Referencias:

  • Abrahám, I., Harkany, T., Horvath, K.M., Veenema, A.H., Penke, B., Nyakas, C., Luiten, P.G.M., Chronic corticosterone administration dose-dependently modulates Aβ (1-42) and NMDA-induced neurodegeneration in rat magnocellular nucleus basalis (2000) J Neuroendocrinol, 12, pp. 486-494
  • Azcoitia, I., Sierra, A., Veiga, S., Garcia-Segura, L.M., Aromatase expression by reactive astroglia is neuroprotective (2003) Ann N Y Acad Sci, 1007, pp. 298-305
  • Balthazart, J., Baillien, M., Ball, G.F., Rapid control of brain aromatase activity by glutamatergic inputs (2006) Endocrinology, 147, pp. 359-366
  • Balthazart, J., Baillien, M., Charlier, T.D., Ball, G.F., Calcium-dependent phosphorylation processes control brain aromatase in quail (2003) Eur J Neurosci, 17, pp. 1591-1606
  • Balthazart, J., Foidart, A., Surlemont, C., Harada, N., Naftolin, F., Neuroanatomical specificity in the autoregulation of aromatase-immunoreactive neurons by androgens and estrogens: an immunocytochemical study (1992) Brain Res, 574, pp. 280-290
  • Barha, C.K., Lieblich, S.E., Galea, L.A., Different forms of oestrogens rapidly upregulate cell proliferation in the dentate gyrus of adult female rats (2009) J Neuroendocrinol, 21, pp. 155-156
  • Bayer, S., Hippocampal region (1985) The rat nervous system Vol 1; forebrain and midbrain, pp. 335-352. , Academic Press, New York, NY, G. Paxinos (Ed.)
  • Behl, C., Estrogen as a neuroprotective hormone (2002) Nat Rev Neurosci, 3, pp. 433-442
  • Bourguiba, S., Lambard, S., Carreau, S., Steroids control the aromatase gene expression in purified germ cells from the adult male rat (2003) J Mol Endocrinol, 31, pp. 83-94
  • Burul-Bozkurt, N., Pekiner, C., Kelicen, P., Diabetes alters aromatase enzyme levels in sciatic nerve and hippocampus tissues of rats (2010) Cell Mol Neurobiol, 30, pp. 445-451
  • Butler, H.T., Warden, D.R., Hogervorst, E., Ragoussis, J., Smith, A.D., Lehmann, D.J., Association of the aromatase gene with Alzheimer's disease in women (2010) Neurosci Lett, 468, pp. 202-206
  • Carswell, H.V., Dominiczak, A.F., Garcia-Segura, L.M., Harada, N., Hutchison, J.B., Macrae, I.M., Brain aromatase expression after experimental stroke: topography and time course (2005) J Steroid Biochem Mol Biol, 96, pp. 89-91
  • Cesi, P.N., Melcangi, R.C., Celotti, F., Martini, L., Distribution of aromatase activity in cultured neurons and glia cells (1993) J Steroid Biochem Mol Biol, 44, pp. 637-639
  • Charlier, T.D., Cornil, C.A., Ball, G.F., Balthazart, J., Diversity of mechanisms involved in aromatase regulation and estrogen action in the brain (2010) Biochim Biophys Acta, 1800, pp. 1094-1105
  • Claiborne, B.J., Amaral, D.G., Cowan, W.M., A light and electron microscopic analysis of the mossy fibers of the rat dentate gyrus (1986) J Comp Neurol, 246, pp. 435-458
  • De Nicola, A.F., Pietranera, L., Beauquis, J., Ferrini, M.G., Saravia, F.E., Steroid protection in aging and age-associated diseases (2009) Exp Gerontol, 44, pp. 34-40
  • De Nicola, A.F., Saravia, F.E., Beauquis, J., Pietranera, L., Ferrini, M.G., Estrogens and neuroendocrine hypothalamic-pituitary-adrenal axis function (2006) Front Horm Res, 35, pp. 157-168
  • 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 immuno-reactivity in hippocampus of aging male rats (1999) Neuroendocrinology, 69, pp. 129-137
  • Garcia-Segura, L.M., Aromatase in the brain: not just for reproduction anymore (2008) J Neuroendocrinol, 20, pp. 705-712
  • Garcia-Segura, L.M., Sanz, A., Mendez, P., Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection (2006) Neuroendocrinology, 84, pp. 275-279
  • Garcia-Segura, L.M., Wozniak, A., Azcoitia, I., Rodriguez, J.R., Hutchison, R.E., Hutchison, J.B., Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair (1999) Neuroscience, 89, pp. 567-578
  • González, S.L., López-Costa, J.J., Labombarda, F., Deniselle, M.C., Guennoun, R., Schumacher, M., De Nicola, A.F., Progesterone effects on neuronal ultrastructure and expression of microtubule-associated protein 2 (MAP2) in rats with acute spinal cord injury (2009) Cell Mol Neurobiol, 29, pp. 27-39
  • Goodman, Y., Bruce, A.J., Cheng, B., Mattson, M.P., Estrogens attenuate and CORT exacerbates excitotoxicity, oxidative injury, and amyloid -peptide toxicity in hippocampal neurons (1996) J Neurochem, 66, pp. 1836-1844
  • Gould, E., Tanapat, P., Rydel, T., Hastings, N., Regulation of hippocampal neurogenesis in adulthood (2000) Biol Psychiatry, 48, pp. 715-720
  • Harada, N., Abe-Dohmae, S., Loeffen, R., Foidart, A., Balthazart, J., Synergism between androgens and estrogens in the induction of aromatase and its messenger RNA inthe brain (1993) Brain Res, 622, pp. 243-256
  • Hennigan, A., Callaghan, C.K., Kealy, J., Rouine, J., Kelly, A.M., Deficits in LTP and recognition memory in the genetically hypertensive rat are associated with decreased expression of neurotrophic factors and their receptors in the dentate gyrus (2009) Behav Brain Res, 197, pp. 371-377
  • Hojo, Y., Higo, S., Ishii, H., Ooishi, Y., Mukai, H., Murakami, G., Kominami, T., Kawato, S., Comparison between hippocampus-synthesized andcirculation-derived sex steroids in the hippocampus (2009) Endocrinology, 150, pp. 5106-5112
  • Iivonen, S., Heikkinen, T., Puolivali, J., Helisalmi, S., Hiltunen, M., Soininen, H., Tanila, H., Effects of estradiol on spatial learning, hippocampal cytochormome P450 19, and estrogen alpha and beta mRNA levels in ovariectomized female mice (2006) Neuroscience, 137, pp. 1143-1152
  • Imaki, T., Naruse, M., Harada, S., Chikada, N., Nakahuma, N., Yoshimoto, T., Demura, H., Stress-induced changes of gene expression in the paraventricular nucleus is enhanced in spontaneously hypertensive rats (1998) J Neuroendocrinol, 10, pp. 633-643
  • Ishunina, T.A., Fischer, D.F., Swaab, D.F., Estrogen receptor alpha and its splice variants in the hippocampus in aging and Alzheimer's disease (2007) Neurobiol Aging, 28, pp. 1670-1681
  • Jesmin, S., Togashi, H., Sakuma, I., Mowa, C.N., Ueno, K., Yamaguchi, T., Yoshioka, M., Kitabatake, A., Gonadal hormones and frontocortical expression of vascular endothelial growth factor in male stroke-prone, spontaneously hypertensive rats, a model for attention-deficit/hyperactivity disorder (2004) Endocrinology, 145, pp. 4330-4343
  • Kronenberg, G., Lippoldt, A., Kempermann, G., Two genetic rat models of arterial hypertension show different mechanisms by which adult hippocampal neurogenesis is increased (2007) Dev Neurosci, 29, pp. 124-133
  • Labombarda, F., Gonzalez, S.L., Gonzalez, D.M., Guennoun, R., Schumacher, M., De Nicola, A.F., Cellular basis for progesterone neuroprotection in the injured spinal cord (2002) Neurotrauma, 19, pp. 343-355
  • Lephart, E.D., A review of aromatase cytochrome P450 (1996) Brain Res Rev, 22, pp. 1-26
  • Li, D.P., Pan, H.L., Glutamatergic inputs in the hypothalamic paraventricular nucleus maintain sympathetic vasomotor tone in hypertension (2007) Hypertension, 49, pp. 916-925
  • Livak, K.J., Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method (2001) Methods, 25, pp. 402-408
  • Luchetti, S., Bossers, K., Van de Bilt, S., Agrapart, V., Morales, R.R., Frajese, G.V., Swaab, D.F., Neurosteroid biosynthetic pathways changes in prefrontal cortex in Alzheimer's disease Neurobiol Aging, , in press
  • Manthey, D., Behl, C., From structural biochemistry to expression profiling: neuroprotective activities of estrogen (2006) Neuroscience, 138, pp. 845-850
  • McCullough, L.D., Hurn, P.D., Estrogen and ischemic neuroprotection: an integrated view (2003) Trends Endocrinol Metab, 14, pp. 228-235
  • McEwen, B.S., Estrogen actions throughout the brain (2002) Recent Prog Horm Res, 57, pp. 357-384
  • 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 U S A, 98, pp. 7093-7100
  • Miyakubo, H., Hayashi, Y., Tanaka, J., Enhanced response of subfornical organ neurons projecting to the hypothalamic paraventricular nucleus to angiotensin II in spontaneously hypertensive rats (2002) Auton Neurosci, 95, pp. 131-136
  • Munetsuna, E., Hojo, Y., Hattori, M., Ishii, H., Kawato, S., Ishida, A., Kominami, S.A., Yamazaki, T., Retinoic acid stimulates 17beta-estradiol and testosterone synthesis in rat hippocampal slice cultures (2009) Endocrinology, 150, pp. 4260-4269
  • Naftolin, F., Horvath, T.L., Jakab, R.L., Leranth, C., Harada, N., Balthazart, J., Aromatase immunoreactivity in axon terminals of the vertebrate brain. An immunocytochemical study on quail, rat, monkey and human tissues (1996) Neuroendocrinology, 63, pp. 149-155
  • Paglieri, C., Bisbocci, D., Caserta, M., Rabbia, F., Bertello, C., Canade, A., Veglio, F., Hypertension and cognitive function (2008) Clin Exp Hypertens, 30, pp. 701-710
  • Pietranera, L., Saravia, F., Gonzalez Deniselle, M.C., Roig, P., Lima, A., De Nicola, A.F., Abnormalities of the hippocampus are similar in deoxycorticosterone acetate-salt hypertensive rats and spontaneously hypertensive rats (2006) J Neuroendocrinol, 18, pp. 466-474
  • Pietranera, L., Saravia, F., Roig, P., Lima, A., De Nicola, A.F., Mineralocorticoid treatment upregulates the hypothalamic vasopressinergic system of spontaneously hypertensive rats (2004) Neuroendocrinology, 80, pp. 100-110
  • Pietranera, L., Saravia, F.E., Roig, P., Lima, A., De Nicola, A.F., Protective effects of estradiol in the brain of rats with genetic or mineralocorticoid-induced hypertension (2008) Psychoneuroendocrinology, 33, pp. 270-281
  • 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
  • Prange-Kiel, J., Rune, G.M., Direct and indirect effects of estrogen on rat hippocampus (2006) Neuroscience, 138, pp. 765-772
  • Prange-Kiel, J., Fester, L., Zhou, L., Jarry, H., Rune, G.M., Estrus cyclicity of spinogenesis: underlying mechanisms (2009) J Neural Transm, 116, pp. 1417-1425
  • Rahmouni, K., Barthelmebs, M., Grima, M., Imbs, J.L., deJong, W., Involvement of brain mineralocorticoid receptor in salt-enhanced hypertension in spontaneously hypertensive rats (2001) Hypertension, 38, pp. 902-906
  • Roselli, C.E., Horton, L.E., Resko, J.A., Distribution and regulation of aromatase activity in the rat hypothalamus and limbic system (1985) Endocrinology, 117, pp. 2471-2477
  • Rune, G.M., Lohse, C., Prange-Kiel, J., Fester, L., Frotscher, M., Synaptic plasticity in the hippocampus: effects of estrogen from the gonads or hippocampus? (2006) Neurochem Res, 31, pp. 145-155
  • Russell, V.A., Increased AMPA receptor function in slices containing the prefrontal cortex of spontaneously hypertensive rats (2001) Metab Brain Dis, 16, pp. 143-149
  • Saavedra, J.M., Benicky, J., Zhou, J., Angiotensin II: multitasking in the brain (2006) J Hypertens Suppl, 24, pp. S131-S137
  • Sabbatini, M., Catalani, A., Consoli, C., Marletta, N., Tomassoni, D., Avola, R., The hippocampus in spontaneously hypertensive rats: an animal model of vascular dementia? (2002) Mech Ageing Dev, 123, pp. 547-559
  • Sabbatini, M., Strocchi, P., Vitaioli, L., Amenta, P., The hippocampus in spontaneously hypertensive rats: a quantitative microanatomical study (2000) Neuroscience, 100, pp. 251-258
  • Saldanha, C.J., Duncan, K.A., Walters, B.J., Neuroprotective actions of brain aromatase (2009) Front Neuroendocrinol, 30, pp. 106-118
  • Saravia, F., Beauquis, J., Pietranera, L., De Nicola, A.F., Neuroprotective effects of estradiol in hippocampal neurons and glia of middle age mice (2007) Psychoneuroendocrinology, 32, pp. 480-492
  • Saravia, F., Revsin, Y., Lux-Lantos, V., Beauquis, J., Homo-Delarche, F., De Nicola, A.F., Oestradiol restores cell proliferation in dentate gyrus and subventricular zone of streptozotocin-diabetic mice (2004) J Neuroendocrinol, 16, pp. 704-710
  • Sarkar, S.N., Huang, R.Q., Logan, S.M., Yi, K.D., Dillon, G.H., Simpkins, J.W., Estrogens directly potentiate neuronal L-type Ca2+ channels (2008) Proc Natl Acad Sci U S A, 105, pp. 15148-151453
  • 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
  • Shimodaira, M., Nakayama, T., Sato, N., Saito, K., Morita, A., Sato, I., Takahashi, T., Izumi, Y., Association study of aromatase gene (CYP19A1) in essential hypertension (2008) Int J Med Sci, 5, pp. 29-35
  • Shughrue, P.J., Lane, M.V., Merchentaler, I., Comparative distribution of estrogen receptor α and β mRNA in the rat central nervous system (1997) J Comp Neurol, 388, pp. 507-525
  • Skup, M., Dwornik, A., Macias, M., Sulejczak, D., Wiater, M., Czarkowska-Bauch, J., Long-term locomotor training up-regulates TrkB(FL) receptor-like proteins, brain-derived neurotrophic factor, and neurotrophin 4 with different topographies of expression in oligodendroglia and neurons in the spinal cord (2002) Exp Neurol, 176, pp. 289-307
  • Spencer, J.L., Waters, E.M., Romeo, R.D., Wood, G.E., Milner, T.A., McEwen, B.S., Uncovering the mechanisms of estrogen effects on hippocampal function (2008) Front Neuroendocrinol, 29, pp. 219-237
  • Strobl-Mazzulla, P.H., Lethimonier, C., Gueguen, M.M., Karube, M., Fernandino, J.I., Yoshizaki, G., Patiño, R., Somoza, G.M., Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: neuroanatomical and functional relations (2008) Gen Comp Endocrinol, 158, pp. 191-201
  • Suzuki, S., Gerhold, L.M., Bottner, M., Rau, S.W., Dela, C.C., Yang, E., Zhu, H., Wise, P.M., Estradiol enhances neurogenesis following ischemic stroke through estrogen receptors alpha and beta (2007) J Comp Neurol, 500, pp. 1064-1075
  • Swanson, L.W., Normal hippocampal circuitry (1982) Neurosci Res Prog Bull, 20, pp. 624-637
  • Tomassoni, D., Avola, R., Di Tullio, A., Sabbatini, M., Vitaioli, L., Amenta, F., Increased expression of glial fibrillary acidic protein in the brain of spontaneously hypertensive rats (2004) Clin Exp Hypertens, 26, pp. 335-350
  • Ueno, M., Sakamoto, H., Tomimoto, H., Akiguchi, I., Onodera, M., Huang, C.-L., Kamenishi, K., Blood-brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats (2004) Acta Neuropathol, 107, pp. 532-538
  • 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
  • Yague, J.G., Azcoitia, I., DeFelipe, J., Garcia-Segura, L.M., Muñoz, A., Aromatase expression in the normal and epileptic human hippocampus (2010) Brain Res, 1315, pp. 41-52
  • Yague, J.G., Garcia-Segura, L.M., Azcoitia, I., Selective transcriptional regulation of aromatase gene by vitamin D, dexamethasone and mifepristone in human glioma cells (2009) Endocrine, 35, pp. 252-261
  • Yague, J.G., Wang, A.C., Janssen, W.G., Hof, P.R., Garcia-Segura, L.M., Azcoitia, I., Morrison, J.H., Aromatase distribution in the monkey temporal neocortex and hippocampus (2008) Brain Res, 1209, pp. 115-127
  • Yilmaz, M.B., Wolfe, A., Cheng, Y.H., Glidewell-Kenney, C., Jameson, J.L., Bulun, S.E., Aromatase promoter If is regulated by estrogen receptor alpha (ESR1) in mouse hypothalamic neuronal cell lines (2009) Biol Reprod, 81, pp. 956-965
  • Zhao, C., Fujinaga, R., Yanai, A., Kokubu, K., Takeshita, Y., Watanabe, Y., Shinoda, K., Sex-steroidal regulation of aromatase mRNA expression in adult male rat brain: a quantitative non-radioactive in situ hybridization study (2008) Cell Tissue Res, 332, pp. 381-391

Citas:

---------- APA ----------
Pietranera, L., Bellini, M.J., Arévalo, M.A., Goya, R., Brocca, M.E., Garcia-Segura, L.M. & De Nicola, A.F. (2011) . Increased aromatase expression in the hippocampus of spontaneously hypertensive rats: Effects of estradiol administration. Neuroscience, 174, 151-159.
http://dx.doi.org/10.1016/j.neuroscience.2010.11.044
---------- CHICAGO ----------
Pietranera, L., Bellini, M.J., Arévalo, M.A., Goya, R., Brocca, M.E., Garcia-Segura, L.M., et al. "Increased aromatase expression in the hippocampus of spontaneously hypertensive rats: Effects of estradiol administration" . Neuroscience 174 (2011) : 151-159.
http://dx.doi.org/10.1016/j.neuroscience.2010.11.044
---------- MLA ----------
Pietranera, L., Bellini, M.J., Arévalo, M.A., Goya, R., Brocca, M.E., Garcia-Segura, L.M., et al. "Increased aromatase expression in the hippocampus of spontaneously hypertensive rats: Effects of estradiol administration" . Neuroscience, vol. 174, 2011, pp. 151-159.
http://dx.doi.org/10.1016/j.neuroscience.2010.11.044
---------- VANCOUVER ----------
Pietranera, L., Bellini, M.J., Arévalo, M.A., Goya, R., Brocca, M.E., Garcia-Segura, L.M., et al. Increased aromatase expression in the hippocampus of spontaneously hypertensive rats: Effects of estradiol administration. Neuroscience. 2011;174:151-159.
http://dx.doi.org/10.1016/j.neuroscience.2010.11.044