Skip to main content
Erschienen in: Endocrine 3/2014

01.08.2014 | Original Article

Effect of low doses of progesterone in the expression of the GABA(A) receptor α4 subunit and procaspase-3 in the hypothalamus of female rats

verfasst von: Bruno D. Arbo, Susie Andrade, Gabriela Osterkamp, Rosane Gomez, Maria Flávia M. Ribeiro

Erschienen in: Endocrine | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

Progesterone is a steroid which regulates neural function, thereby modulating neurotransmission, cell survival, and behavior. Previous studies by our group have shown that chronic administration of low doses of progesterone in diestrus II female rats has an antidepressant-like effect in the forced swimming test (FST). Depression is associated with the several neurotransmitters systems, including GABA and serotonin, and with neurodegeneration and cell death in some brain circuits. The aim of this study was to verify the effect of progesterone on the protein expression of the GABA(A) receptor α4 subunit, serotonin transporter (SERT), Akt, extracellular signal-regulated kinase (Erk), and caspase-3 in the hypothalamus of diestrus II female rats exposed to the FST. Female rats were treated with a daily injection of progesterone (0.4 mg/kg) or vehicle, during two complete oestrous cycles. On the day of the experiment, the animals were euthanized 30 min after the FST, the hypothalamus was dissected and protein expression of GABA(A) receptor α4 subunit, SERT, Akt, Erk, and caspase-3 was evaluated. Progesterone increased the expression of GABA(A) receptor α4 subunit but did not change the expression of SERT. Progesterone decreased the expression of procaspase-3 in the hypothalamus without changing the activation of Akt and Erk in this structure. In summary, our results suggest that progesterone acts to increase the expression of the GABA(A) receptor α4 subunit and decrease the expression of procaspase-3 in the hypothalamus of female rats. Such effects may be involved in the antidepressant-like effect of progesterone in female rats exposed to the FST.
Literatur
1.
Zurück zum Zitat B. Dubrovsky, Neurosteroids, neuroactive steroids, and symptoms of affective disorders. Pharmacol. Biochem. Behav. 84, 644–655 (2006)PubMedCrossRef B. Dubrovsky, Neurosteroids, neuroactive steroids, and symptoms of affective disorders. Pharmacol. Biochem. Behav. 84, 644–655 (2006)PubMedCrossRef
2.
Zurück zum Zitat Z. Amin, G.F. Mason, I. Cavus, J.H. Krystal, D.L. Rothman, C.N. Epperson, The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women. Pharmacol. Biochem. Behav. 84, 635–643 (2006)PubMedCrossRef Z. Amin, G.F. Mason, I. Cavus, J.H. Krystal, D.L. Rothman, C.N. Epperson, The interaction of neuroactive steroids and GABA in the development of neuropsychiatric disorders in women. Pharmacol. Biochem. Behav. 84, 635–643 (2006)PubMedCrossRef
3.
Zurück zum Zitat A.L. Morrow, Recent developments in the significance and therapeutic relevance of neuroactive steroids—introduction to the special issue. Pharmacol. Ther. 116, 1–6 (2007)PubMedCentralPubMedCrossRef A.L. Morrow, Recent developments in the significance and therapeutic relevance of neuroactive steroids—introduction to the special issue. Pharmacol. Ther. 116, 1–6 (2007)PubMedCentralPubMedCrossRef
4.
Zurück zum Zitat S. Andrade, B.D. Arbo, B.A. Batista, A.M. Neves, G. Branchini, I.S. Brum, H.M. Barros, R. Gomez, M.F. Ribeiro, Effect of progesterone on the expression of GABA(A) receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere. Cell Biochem. Funct. 30, 696–700 (2012)PubMedCrossRef S. Andrade, B.D. Arbo, B.A. Batista, A.M. Neves, G. Branchini, I.S. Brum, H.M. Barros, R. Gomez, M.F. Ribeiro, Effect of progesterone on the expression of GABA(A) receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere. Cell Biochem. Funct. 30, 696–700 (2012)PubMedCrossRef
5.
Zurück zum Zitat S. Andrade, S.L. Silveira, B.D. Arbo, B.A. Batista, R. Gomez, H.M. Barros, M.F. Ribeiro, Sex-dependent antidepressant effects of lower doses of progesterone in rats. Physiol. Behav. 99, 687–690 (2010)PubMedCrossRef S. Andrade, S.L. Silveira, B.D. Arbo, B.A. Batista, R. Gomez, H.M. Barros, M.F. Ribeiro, Sex-dependent antidepressant effects of lower doses of progesterone in rats. Physiol. Behav. 99, 687–690 (2010)PubMedCrossRef
6.
Zurück zum Zitat R. Cossart, C. Bernard, Y. Ben-Ari, Multiple facets of GABAergic neurons and synapses: multiple fates of GABA signalling in epilepsies. Trends Neurosci. 28, 108–115 (2005)PubMedCrossRef R. Cossart, C. Bernard, Y. Ben-Ari, Multiple facets of GABAergic neurons and synapses: multiple fates of GABA signalling in epilepsies. Trends Neurosci. 28, 108–115 (2005)PubMedCrossRef
7.
Zurück zum Zitat D. Chandra, F. Jia, J. Liang, Z. Peng, A. Suryanarayanan, D.F. Werner, I. Spigelman, C.R. Houser, R.W. Olsen, N.L. Harrison, G.E. Homanics, GABAA receptor alpha 4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol. Proc. Natl. Acad. Sci. USA 103, 15230–15235 (2006)PubMedCentralPubMedCrossRef D. Chandra, F. Jia, J. Liang, Z. Peng, A. Suryanarayanan, D.F. Werner, I. Spigelman, C.R. Houser, R.W. Olsen, N.L. Harrison, G.E. Homanics, GABAA receptor alpha 4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol. Proc. Natl. Acad. Sci. USA 103, 15230–15235 (2006)PubMedCentralPubMedCrossRef
8.
Zurück zum Zitat J. Liang, N. Zhang, E. Cagetti, C.R. Houser, R.W. Olsen, I. Spigelman, Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors. J. Neurosci. 26, 1749–1758 (2006)PubMedCrossRef J. Liang, N. Zhang, E. Cagetti, C.R. Houser, R.W. Olsen, I. Spigelman, Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors. J. Neurosci. 26, 1749–1758 (2006)PubMedCrossRef
9.
Zurück zum Zitat S.S. Smith, H. Shen, Q.H. Gong, X. Zhou, Neurosteroid regulation of GABA(A) receptors: focus on the alpha4 and delta subunits. Pharmacol. Ther. 116, 58–76 (2007)PubMedCentralPubMedCrossRef S.S. Smith, H. Shen, Q.H. Gong, X. Zhou, Neurosteroid regulation of GABA(A) receptors: focus on the alpha4 and delta subunits. Pharmacol. Ther. 116, 58–76 (2007)PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat M. Gulinello, Q.H. Gong, X. Li, S.S. Smith, Short-term exposure to a neuroactive steroid increases alpha4 GABA(A) receptor subunit levels in association with increased anxiety in the female rat. Brain Res. 910, 55–66 (2001)PubMedCrossRef M. Gulinello, Q.H. Gong, X. Li, S.S. Smith, Short-term exposure to a neuroactive steroid increases alpha4 GABA(A) receptor subunit levels in association with increased anxiety in the female rat. Brain Res. 910, 55–66 (2001)PubMedCrossRef
11.
Zurück zum Zitat H. Shen, Q.H. Gong, M. Yuan, S.S. Smith, Short-term steroid treatment increases delta GABAA receptor subunit expression in rat CA1 hippocampus: pharmacological and behavioral effects. Neuropharmacology 49, 573–586 (2005)PubMedCentralPubMedCrossRef H. Shen, Q.H. Gong, M. Yuan, S.S. Smith, Short-term steroid treatment increases delta GABAA receptor subunit expression in rat CA1 hippocampus: pharmacological and behavioral effects. Neuropharmacology 49, 573–586 (2005)PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat A. Cipriani, T.A. Furukawa, J.R. Geddes, L. Malvini, A. Signoretti, H. McGuire, R. Churchill, A. Nakagawa, C. Barbui, MANGA Study Group: does randomized evidence support sertraline as first-line antidepressant for adults with acute major depression? A systematic review and meta-analysis. J. Clin. Psychiatry 69, 1732–1742 (2008)PubMedCrossRef A. Cipriani, T.A. Furukawa, J.R. Geddes, L. Malvini, A. Signoretti, H. McGuire, R. Churchill, A. Nakagawa, C. Barbui, MANGA Study Group: does randomized evidence support sertraline as first-line antidepressant for adults with acute major depression? A systematic review and meta-analysis. J. Clin. Psychiatry 69, 1732–1742 (2008)PubMedCrossRef
13.
Zurück zum Zitat G. Attali, A. Weizman, I. Gil-Ad, M. Rehavi, Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters. Brain Res. 756, 153–159 (1997)PubMedCrossRef G. Attali, A. Weizman, I. Gil-Ad, M. Rehavi, Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters. Brain Res. 756, 153–159 (1997)PubMedCrossRef
14.
Zurück zum Zitat S. Benmansour, R.S. Weaver, A.K. Barton, O.S. Adeniji, A. Frazer, Comparison of the effects of estradiol and progesterone on serotonergic function. Biol. Psychiatry 71, 633–641 (2012)PubMedCentralPubMedCrossRef S. Benmansour, R.S. Weaver, A.K. Barton, O.S. Adeniji, A. Frazer, Comparison of the effects of estradiol and progesterone on serotonergic function. Biol. Psychiatry 71, 633–641 (2012)PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat S. Campbell, G. Macqueen, An update on regional brain volume differences associated with mood disorders. Curr Opin Psychiatry 19, 25–33 (2006)PubMedCrossRef S. Campbell, G. Macqueen, An update on regional brain volume differences associated with mood disorders. Curr Opin Psychiatry 19, 25–33 (2006)PubMedCrossRef
16.
Zurück zum Zitat K.F. Manaye, D.L. Lei, Y. Tizabi, M.I. Dávila-García, P.R. Mouton, P.H. Kelly, Selective neuron loss in the paraventricular nucleus of hypothalamus in patients suffering from major depression and bipolar disorder. J. Neuropathol. Exp. Neurol. 64, 224–229 (2005)PubMed K.F. Manaye, D.L. Lei, Y. Tizabi, M.I. Dávila-García, P.R. Mouton, P.H. Kelly, Selective neuron loss in the paraventricular nucleus of hypothalamus in patients suffering from major depression and bipolar disorder. J. Neuropathol. Exp. Neurol. 64, 224–229 (2005)PubMed
17.
Zurück zum Zitat A.M. Bao, G. Meynen, D.F. Swaab, The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res. Rev. 57, 531–553 (2008)PubMedCrossRef A.M. Bao, G. Meynen, D.F. Swaab, The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res. Rev. 57, 531–553 (2008)PubMedCrossRef
18.
Zurück zum Zitat D.N. Bryant, L.C. Sheldahl, L.K. Marriott, R.A. Shapiro, D.M. Dorsa, Multiple pathways transmit neuroprotective effects of gonadal steroids. Endocrine 29, 199–207 (2006)PubMedCrossRef D.N. Bryant, L.C. Sheldahl, L.K. Marriott, R.A. Shapiro, D.M. Dorsa, Multiple pathways transmit neuroprotective effects of gonadal steroids. Endocrine 29, 199–207 (2006)PubMedCrossRef
19.
Zurück zum Zitat G.E. Hoffman, I. Merchenthaler, S.L. Zup, Neuroprotection by ovarian hormones in animal models of neurological disease. Endocrine 29, 217–231 (2006)PubMedCrossRef G.E. Hoffman, I. Merchenthaler, S.L. Zup, Neuroprotection by ovarian hormones in animal models of neurological disease. Endocrine 29, 217–231 (2006)PubMedCrossRef
20.
Zurück zum Zitat Y. Tokuyama, A.P. Reddy, C.L. Bethea, Neuroprotective actions of ovarian hormones without insult in the raphe region of rhesus macaques. Neuroscience 154, 720–731 (2008)PubMedCentralPubMedCrossRef Y. Tokuyama, A.P. Reddy, C.L. Bethea, Neuroprotective actions of ovarian hormones without insult in the raphe region of rhesus macaques. Neuroscience 154, 720–731 (2008)PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Y. Fan, H. Chen, B. Qiao, L. Luo, H. Ma, H. Li, J. Jiang, D. Niu, Z. Yin, Opposing effects of ERK and p38 MAP kinases on HeLa cell apoptosis induced by dipyrithione. Mol. Cells 23, 30–38 (2007)PubMed Y. Fan, H. Chen, B. Qiao, L. Luo, H. Ma, H. Li, J. Jiang, D. Niu, Z. Yin, Opposing effects of ERK and p38 MAP kinases on HeLa cell apoptosis induced by dipyrithione. Mol. Cells 23, 30–38 (2007)PubMed
22.
Zurück zum Zitat R.D. Porsolt, G. Anton, N. Blavet, M. Jalfre, Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur. J. Pharmacol. 47, 379–391 (1978)PubMedCrossRef R.D. Porsolt, G. Anton, N. Blavet, M. Jalfre, Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur. J. Pharmacol. 47, 379–391 (1978)PubMedCrossRef
23.
Zurück zum Zitat R.D. Porsolt, Behavioral despair, in Antidepressants: neurochemical, behavioral, and clinical perspectives, ed. by S.J. Enna (Raven Press, New York, 1981), pp. 121–139 R.D. Porsolt, Behavioral despair, in Antidepressants: neurochemical, behavioral, and clinical perspectives, ed. by S.J. Enna (Raven Press, New York, 1981), pp. 121–139
24.
Zurück zum Zitat D. da R. Janner, M.H. Jacob, M.P. Jahn, L.C. Kucharski, M.F. Ribeiro, Dehydroepiandrosterone effects on Akt signaling modulation in central nervous system of young and aged healthy rats. J. Steroid Biochem. Mol. Biol. 122, 142–148 (2010)CrossRef D. da R. Janner, M.H. Jacob, M.P. Jahn, L.C. Kucharski, M.F. Ribeiro, Dehydroepiandrosterone effects on Akt signaling modulation in central nervous system of young and aged healthy rats. J. Steroid Biochem. Mol. Biol. 122, 142–148 (2010)CrossRef
25.
Zurück zum Zitat M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal. Biochem. 72, 248–254 (1976)PubMedCrossRef M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal. Biochem. 72, 248–254 (1976)PubMedCrossRef
26.
27.
Zurück zum Zitat P. Follesa, F. Biggio, G. Talani, L. Murru, M. Serra, E. Sanna, G. Biggio, Neurosteroids, GABAA receptors, and ethanol dependence. Psychopharmacology 186, 267–280 (2006)PubMedCrossRef P. Follesa, F. Biggio, G. Talani, L. Murru, M. Serra, E. Sanna, G. Biggio, Neurosteroids, GABAA receptors, and ethanol dependence. Psychopharmacology 186, 267–280 (2006)PubMedCrossRef
28.
Zurück zum Zitat J.L. Griffiths, T.A. Lovick, GABAergic neurones in the rat periaqueductal grey matter express alpha4, beta1 and delta GABAA receptor subunits: plasticity of expression during the estrous cycle. Neuroscience 136, 457–466 (2005)PubMedCrossRef J.L. Griffiths, T.A. Lovick, GABAergic neurones in the rat periaqueductal grey matter express alpha4, beta1 and delta GABAA receptor subunits: plasticity of expression during the estrous cycle. Neuroscience 136, 457–466 (2005)PubMedCrossRef
29.
Zurück zum Zitat F.C. Hsu, R. Waldeck, D.S. Faber, S.S. Smith, Neurosteroid effects on GABAergic synaptic plasticity in hippocampus. J. Neurophysiol. 89, 1929–1940 (2003)PubMedCentralPubMedCrossRef F.C. Hsu, R. Waldeck, D.S. Faber, S.S. Smith, Neurosteroid effects on GABAergic synaptic plasticity in hippocampus. J. Neurophysiol. 89, 1929–1940 (2003)PubMedCentralPubMedCrossRef
30.
Zurück zum Zitat M.S. Nin, F.B. Salles, L.A. Azeredo, A.P. Frazon, R. Gomez, H.M. Barros, Antidepressant effect and changes of GABAA receptor gamma2 subunit mRNA after hippocampal administration of allopregnanolone in rats. J. Psychopharmacol. 22, 477–485 (2008)PubMedCrossRef M.S. Nin, F.B. Salles, L.A. Azeredo, A.P. Frazon, R. Gomez, H.M. Barros, Antidepressant effect and changes of GABAA receptor gamma2 subunit mRNA after hippocampal administration of allopregnanolone in rats. J. Psychopharmacol. 22, 477–485 (2008)PubMedCrossRef
31.
Zurück zum Zitat S.S. Smith, Q.H. Gong, F.C. Hsu, R.S. Markowitz, J.M. ffrench-Mullen, X. Li, GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature 392, 926–930 (1998)PubMedCrossRef S.S. Smith, Q.H. Gong, F.C. Hsu, R.S. Markowitz, J.M. ffrench-Mullen, X. Li, GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature 392, 926–930 (1998)PubMedCrossRef
32.
Zurück zum Zitat R.C. Pierson, A.M. Lyons, L.J. Greenfield Jr., Gonadal steroids regulate GABAA receptor subunit mRNA expression in NT2-N neurons. Brain Res. Mol. Brain Res. 138, 105–115 (2005)PubMedCrossRef R.C. Pierson, A.M. Lyons, L.J. Greenfield Jr., Gonadal steroids regulate GABAA receptor subunit mRNA expression in NT2-N neurons. Brain Res. Mol. Brain Res. 138, 105–115 (2005)PubMedCrossRef
33.
Zurück zum Zitat A. Kuver, H. Shen, S.S. Smith, Regulation of the surface expression of α4β2δ GABAA receptors by high efficacy states. Brain Res. 1463, 1–20 (2012)PubMedCentralPubMedCrossRef A. Kuver, H. Shen, S.S. Smith, Regulation of the surface expression of α4β2δ GABAA receptors by high efficacy states. Brain Res. 1463, 1–20 (2012)PubMedCentralPubMedCrossRef
34.
Zurück zum Zitat N. Sabaliauskas, H. Shen, G.E. Homanics, S.S. Smith, C. Aoki, Knockout of the γ-aminobutyric acid receptor subunit α4 reduces functional δ-containing extrasynaptic receptors in hippocampal pyramidal cells at the onset of puberty. Brain Res. 1450, 11–23 (2012)PubMedCentralPubMedCrossRef N. Sabaliauskas, H. Shen, G.E. Homanics, S.S. Smith, C. Aoki, Knockout of the γ-aminobutyric acid receptor subunit α4 reduces functional δ-containing extrasynaptic receptors in hippocampal pyramidal cells at the onset of puberty. Brain Res. 1450, 11–23 (2012)PubMedCentralPubMedCrossRef
35.
Zurück zum Zitat J. Sarkar, S. Wakefield, G. MacKenzie, S.J. Moss, J. Maguire, Neurosteroidogenesis is required for the physiological response to stress: role of neurosteroid-sensitive GABAA receptors. J. Neurosci. 31, 18198–18210 (2011)PubMedCentralPubMedCrossRef J. Sarkar, S. Wakefield, G. MacKenzie, S.J. Moss, J. Maguire, Neurosteroidogenesis is required for the physiological response to stress: role of neurosteroid-sensitive GABAA receptors. J. Neurosci. 31, 18198–18210 (2011)PubMedCentralPubMedCrossRef
36.
Zurück zum Zitat E.R. de Kloet, M. Joëls, F. Holsboer, Stress and the brain: from adaptation to disease. Nat. Rev. Neurosci. 6, 463–475 (2005)PubMedCrossRef E.R. de Kloet, M. Joëls, F. Holsboer, Stress and the brain: from adaptation to disease. Nat. Rev. Neurosci. 6, 463–475 (2005)PubMedCrossRef
37.
Zurück zum Zitat V. Uzunova, Y. Sheline, J.M. Davis, A. Rasmusson, D.P. Uzunov, E. Costa, A. Guidotti, Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc. Natl. Acad. Sci. USA 95, 3239–3244 (1998)PubMedCentralPubMedCrossRef V. Uzunova, Y. Sheline, J.M. Davis, A. Rasmusson, D.P. Uzunov, E. Costa, A. Guidotti, Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc. Natl. Acad. Sci. USA 95, 3239–3244 (1998)PubMedCentralPubMedCrossRef
38.
Zurück zum Zitat M.S. Nin, L.A. Martinez, F. Pibiri, M. Nelson, G. Pinna, Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression. Front. Endocrinol. (Lausanne) 2, 73 (2011) M.S. Nin, L.A. Martinez, F. Pibiri, M. Nelson, G. Pinna, Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression. Front. Endocrinol. (Lausanne) 2, 73 (2011)
39.
Zurück zum Zitat N.Z. Lu, A.J. Eshleman, A. Janowsky, C.L. Bethea, Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques. Mol. Psychiatry 8, 353–360 (2003)PubMedCrossRef N.Z. Lu, A.J. Eshleman, A. Janowsky, C.L. Bethea, Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques. Mol. Psychiatry 8, 353–360 (2003)PubMedCrossRef
40.
Zurück zum Zitat C.L. Bethea, A.P. Reddy, Y. Tokuyama, J.A. Henderson, F.B. Lima, Protective actions of ovarian hormones in the serotonin system of macaques. Front. Neuroendocrinol. 30, 212–238 (2009)PubMedCentralPubMedCrossRef C.L. Bethea, A.P. Reddy, Y. Tokuyama, J.A. Henderson, F.B. Lima, Protective actions of ovarian hormones in the serotonin system of macaques. Front. Neuroendocrinol. 30, 212–238 (2009)PubMedCentralPubMedCrossRef
41.
Zurück zum Zitat M. Maes, R. Yirmyia, J. Noraberg, S. Brene, J. Hibbeln, G. Perini, M. Kubera, P. Bob, B. Lerer, M. Maj, The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab. Brain Dis. 24, 27–53 (2009)PubMedCrossRef M. Maes, R. Yirmyia, J. Noraberg, S. Brene, J. Hibbeln, G. Perini, M. Kubera, P. Bob, B. Lerer, M. Maj, The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab. Brain Dis. 24, 27–53 (2009)PubMedCrossRef
42.
Zurück zum Zitat C. Guerra-Araiza, M.A. Amorim, R. Pinto-Almazán, A. González-Arenas, M.G. Campos, L.M. Garcia-Segura, Regulation of the phosphoinositide-3 kinase and mitogen-activated protein kinase signaling pathways by progesterone and its reduced metabolites in the rat brain. J. Neurosci. Res. 87, 470–481 (2009)PubMedCrossRef C. Guerra-Araiza, M.A. Amorim, R. Pinto-Almazán, A. González-Arenas, M.G. Campos, L.M. Garcia-Segura, Regulation of the phosphoinositide-3 kinase and mitogen-activated protein kinase signaling pathways by progesterone and its reduced metabolites in the rat brain. J. Neurosci. Res. 87, 470–481 (2009)PubMedCrossRef
43.
Zurück zum Zitat X. Wang, The expanding role of mitochondria in apoptosis. Genes Dev. 15, 2922–2933 (2001)PubMed X. Wang, The expanding role of mitochondria in apoptosis. Genes Dev. 15, 2922–2933 (2001)PubMed
44.
Zurück zum Zitat M. Kubera, E. Obuchowicz, L. Goehler, J. Brzeszcz, M. Maes, In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 35, 744–759 (2011)PubMedCrossRef M. Kubera, E. Obuchowicz, L. Goehler, J. Brzeszcz, M. Maes, In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog. Neuropsychopharmacol. Biol. Psychiatry 35, 744–759 (2011)PubMedCrossRef
45.
Zurück zum Zitat V.D. Nair, C.W. Olanow, Differential modulation of Akt/glycogen synthase kinase-3beta pathway regulates apoptotic and cytoprotective signaling responses. J. Biol. Chem. 283, 15469–15478 (2008)PubMedCentralPubMedCrossRef V.D. Nair, C.W. Olanow, Differential modulation of Akt/glycogen synthase kinase-3beta pathway regulates apoptotic and cytoprotective signaling responses. J. Biol. Chem. 283, 15469–15478 (2008)PubMedCentralPubMedCrossRef
46.
Zurück zum Zitat C. Tang, Y.H. Lu, J.H. Xie, F. Wang, J.N. Zou, J.S. Yang, Y.Y. Xing, T. Xi, Downregulation of survivin and activation of caspase-3 through the PI3 K/Akt pathway in ursolic acid-induced HepG2 cell apoptosis. Anticancer Drugs 20, 249–258 (2009)PubMedCrossRef C. Tang, Y.H. Lu, J.H. Xie, F. Wang, J.N. Zou, J.S. Yang, Y.Y. Xing, T. Xi, Downregulation of survivin and activation of caspase-3 through the PI3 K/Akt pathway in ursolic acid-induced HepG2 cell apoptosis. Anticancer Drugs 20, 249–258 (2009)PubMedCrossRef
47.
Zurück zum Zitat W. Hu, T. Shen, M.H. Wang, Cell cycle arrest and apoptosis induced by methyl 3,5-dicaffeoyl quinate in human colon cancer cells: involvement of the PI3 K/Akt and MAP kinase pathways. Chem. Biol. Interact. 194, 48–57 (2011)PubMedCrossRef W. Hu, T. Shen, M.H. Wang, Cell cycle arrest and apoptosis induced by methyl 3,5-dicaffeoyl quinate in human colon cancer cells: involvement of the PI3 K/Akt and MAP kinase pathways. Chem. Biol. Interact. 194, 48–57 (2011)PubMedCrossRef
Metadaten
Titel
Effect of low doses of progesterone in the expression of the GABA(A) receptor α4 subunit and procaspase-3 in the hypothalamus of female rats
verfasst von
Bruno D. Arbo
Susie Andrade
Gabriela Osterkamp
Rosane Gomez
Maria Flávia M. Ribeiro
Publikationsdatum
01.08.2014
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 3/2014
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-013-0126-5

Weitere Artikel der Ausgabe 3/2014

Endocrine 3/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.