The decrease in JNK- and p38-MAP kinase activity is accompanied by the enhancement of PP2A phosphatase level in the brain of prenatally stressed rats

• Autorzy: Budziszewska B. , Szymanska M. , Leskiewicz M. , Basta-Kaim A. , Jaworska-Feil L. , Kubera M. , Jantas D. , Lason W.
• Języki publikacji: EN

Abstrakty

EN

Our previous study suggests that in prenatal stress model of depression glucocorticoid receptor (GR) function in adult rats is enhanced. However, the long-term consequences of stress, a causal factor in depression, on intracellular elements involved into the regulation of GR function is poorly examined. Mitogen-activated protein kinases (MAPKs), activity of which is disturbed in depression, are important regulators of GR action, so they can mediate the effect of stress on GR function. Therefore, the aim of the present study was to investigate the levels of active phosphorylated forms of extracellular signal-regulated kinases (ERK), Jun N-terminal kinases (JNK) and the p38 kinase in the hippocampus and frontal cortex in rats subjected to prenatal stress. The concentration of MAP kinase phosphatase (MKP-1, MKP-2) and protein phosphatase-2A (PP2A), which dephosphorylate all forms of MAP kinases, were also determined. During verification of the applied model of depression, we found that prenatally stressed rats displayed high level of immobility in the Porsolt test and that the administration of imipramine, fluoxetine, mirtazapine and tianeptine for 21 days normalized this parameter. Western blot study revealed that rats subjected to prenatal stress had decreased levels of p-JNK1 and p-JNK2 in the hippocampus and p-p38 in the frontal cortex, but the concentrations of p-ERK1 and p-ERK2 were not changed. Chronic treatment with imipramine inhibited the stress-induced decrease in p-JNK1/2, while imipramine, fluoxetine and mirtazapine blocked changes in p-p38. PP2A phosphatase level was higher in the hippocampus and frontal cortex in prenatally stressed animals than in control rats. Chronic treatment with antidepressant drugs attenuated the stress-induced increase in the level of this phosphatase, but had no effect on its concentration in control animals. There was no significant difference in MKP-1 and in MKP-2 levels in both brain structures between control and prenatally stressed rats. The obtained results showed that prenatal stress decreased the levels of active form of JNK and p38, but enhanced PP2A phosphatase expression and most of these changes were reversed by antidepressant drugs. Since p-JNK and p-p38 are known to inhibit GR function their lowered levels may enhance glucocorticoid action. Furthermore, the increased PP2A concentration may intensify GR action not only by inhibition of JNK and p38 phosphorylation, but also by a direct influence on the process of GR translocation.

Słowa kluczowe

EN

PP2A phosphatase; antidepressant drug; depression; extracellular signal-regulated kinase; glucocorticoid receptor; hypothalamic-pituitary-adrenocortical axis; mitogen-activated protein kinase; neurotransmission; p38 kinase; prenatal stress; protein phosphatase; rat; synaptic plasticity

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 2
• Opis fizyczny: p.207-215,fig.,ref.

Twórcy

autor

Budziszewska B.

• Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland

autor

Szymanska M.

autor

Leskiewicz M.

autor

Basta-Kaim A.

autor

Jaworska-Feil L.

autor

Kubera M.

autor

Jantas D.

autor

Lason W.

Bibliografia

• Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 2000; 23: 477-501.
• Holsboer F, Barden N. Antidepressants and hypothalamic-pituitary-adrenocortical regulation. Endocr Rev 1996; 17: 187-205.
• Tokarski K, Pitra P, Duszynska B, Hess G. Imipramine counteracts corticosterone-induced alterations in the effects of the activation of 5-HT(7) receptors in rat hippocampus. J Physiol Pharmacol 2009; 60: 83-88.
• Barbazanges A, Piazza PV, Le Moal M, Maccari S. Maternal glucocorticoid secretion mediates long-term effects of prenatal stress. J Neurosci 1996; 16: 3943-3949.
• Koehl M, Darnaudery M, Dulluc J, Van Reeth O, Le Moal M, Maccari S. Prenatal stress alters circadian activity of hypothalamo-pituitary-adrenal axis and hippocampal corticosteroid receptors in adult rats of both gender. J Neurobiol 1999; 40: 302-315.
• Rao U, McGinty DJ, Shinde A, McCracken JT, Poland RE. Prenatal stress is associated with depression-related electroencephalographic sleep changes in adult male rats: a preliminary report. Prog Neuropsychopharmacol Biol Psychiatry 1999; 23: 929-939.
• Rhees RW, Al-Saleh HN, Kinghorn EW, Fleming DE, Lephart ED. Relationship between sexual behavior and sexually dimorphic structures in the anterior hypothalamus in control and prenatally stressed male rats. Brain Res Bull 1999; 50: 193-199.
• Lemaire V, Koehl M, Le Moal M, Abrous DN. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci USA 2000; 97: 11032-11037.
• Morley-Fletcher S, Darnaudery M, Koehl M, Casolini P, Van Reeth O, Maccari S. Prenatal stress in rats predicts immobility behavior in the forced swim test. Effects of a chronic treatment with tianeptine. Brain Res 2003; 989: 246-251.
• Morley-Fletcher S, Darnaudery M, Mocaer E, et al. Chronic treatment with imipramine reverses immobility behaviour, hippocampal corticosteroid receptors and cortical 5-HT(1A) receptor mRNA in prenatally stressed rats. Neuropharmacology 2004; 47: 841-847.
• Szymanska M, Budziszewska B, Jaworska-Feil L, et al. The effect of antidepressant drugs on the HPA axis activity, glucocorticoid receptor level and FKBP51 concentration in prenatally stressed rats. Psychoneuroendocrinology 2009; 34: 822-832.
• Krstic MD, Rogatsky I, Yamamoto KR, Garabedian MJ. Mitogen-activated and cyclin-dependent protein kinases selectively and differentially modulate transcriptional enhancement by the glucocorticoid receptor. Mol Cell Biol 1997; 17: 3947-3954.
• Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN. Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J Neurochem 2001; 77: 916-928.
• Feng P, Guan Z, Yang X, Fang J. Impairments of ERK signal transduction in the brain in a rat model of depression induced by neonatal exposure of clomipramine. Brain Res 2003; 991: 195-205.
• Gourley SL, Wu FJ, Kiraly DD, et al. Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression. Biol Psychiatry 2008; 63: 353-359.
• Rogatsky I, Logan SK, Garabedian MJ. Antagonism of glucocorticoid receptor transcriptional activation by the c-Jun N-terminal kinase. Proc Natl Acad Sci USA 1998; 95: 2050-2055.
• Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol 2002; 109: 649-657.
• Kassel O, Sancono A, Kratzschmar J, Kreft B, Stassen M, Cato AC. Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1. EMBO J 2001; 20: 7108-7116.
• DeFranco DB, Qi M, Borror KC, Garabedian MJ, Brautigan DL. Protein phosphatase types 1 and/or 2A regulate nucleocytoplasmic shuttling of glucocorticoid receptors. Mol Endocrinol 1991; 5: 1215-1228.
• Bauman AL, Apparsundaram S, Ramamoorthy S, Wadzinski BE, Vaughan RA, Blakely RD. Cocaine and antidepressant-sensitive biogenic amine transporters exist in regulated complexes with protein phosphatase 2A. J Neurosci 2000; 20: 7571-7578.
• Saraf A, Virshup DM, Strack S. Differential expression of the B’beta regulatory subunit of protein phosphatase 2A modulates tyrosine hydroxylase phosphorylation and catecholamine synthesis. J Biol Chem 2007; 282: 573-580.
• Qi X, Lin W, Li J, et al. Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress. Neurobiol Dis 2008; 31: 278-285.
• Bartholoma P, Erlandsson N, Kaufmann K, et al. Neuronal cell death induced by antidepressants: lack of correlation with Egr-1, NF-kappa B and extracellular signal-regulated protein kinase activation. Biochem Pharmacol 2002; 63: 1507-1516.
• Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978; 47: 379-391.
• Chiu K, Lau WM, Lau HT, So KF, Chang RC. Micro-dissection of rat brain for RNA or protein extraction from specific brain region. J Vis Exp 2007; 7: 269.
• Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275.
• Fujioka A, Fujioka T, Ishida Y, Maekawa T, Nakamura S. Differential effects of prenatal stress on the morphological maturation of hippocampal neurons. Neuroscience 2006; 141: 907-915.
• Wang X, Wu H, Lakdawala VS, Hu F, Hanson ND, Miller AH. Inhibition of Jun N-terminal kinase (JNK) enhances glucocorticoid receptor-mediated function in mouse hippocampal HT22 cells. Neuropsychopharmacology 2005; 30: 242-249.
• Otczyk M, Mulik K, Budziszewska B, et al. W. Effect of some antidepressants on the low corticosterone concentration-induced gene transcription in LMCAT fibroblast cells. J Physiol Pharmacol 2008; 59: 153-162.
• Spiliotaki M, Salpeas V, Malitas P, Alevizos V, Moutsatsou P. Altered glucocorticoid receptor signaling cascade in lymphocytes of bipolar disorder patients. Psychoneuroendocrinology 2006; 31: 748-760.
• Szatmary Z, Garabedian MJ, Vilcek J. Inhibition of glucocorticoid receptor-mediated transcriptional activation by p38 mitogen-activated protein (MAP) kinase. J Biol Chem 2004; 279: 43708-43715.
• Chou CT, He S, Jan CR. Paroxetine-induced apoptosis in human osteosarcoma cells: activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation. Toxicol Appl Pharmacol 2007; 218: 265-273.
• Qi X, Lin W, Li J, Pan Y, Wang W. The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress. Behav Brain Res 2006; 175: 233-240.
• Lin CF, Chen CL, Chiang CW, Jan MS, Huang WC, Lin YS. GSK-3b acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 in ceramide-induced mitochondrial apoptosis. J Cell Sci 2007; 120: 2935-2943.
• Szymanska M, Suska A, Budziszewska B, et al. Prenatal stress decreases glycogen synthase kinase-3 phosphorylation in the rat frontal cortex. Pharmacol Rep 2009; 61: 612-620.
• Cheung J, Smith DF. Molecular chaperone interactions with steroid receptors: an update. Mol Endocrinol 2000; 14: 939-946.
• Wochnik GM, Ruegg J, Abel GA, Schmidt U, Holsboer F, Rein T. FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem 2005; 280: 4609-4616.
• Zhang X, Clark AF, YorioT. FK506-binding protein 51 regulates nuclear transport of the glucocorticoid receptor beta and glucocorticoid responsiveness. Invest Ophthalmol Vis Sci 2008; 49: 1037-1047.