Abstract
Corticosterone (CORT) is a kind of corticosteroid produced by cortex of adrenal glands. Hypothalamic–pituitary–adrenal (HPA) axis hyperfunction leads to excessive CORT, which is associated with depression. Few studies have investigated the role of CORT in voltage-gated ion channels and its upstream signaling pathway in central nervous system. In this study, we investigated the mechanism of excessive CORT resulting in brain impairment on voltage-gated ion channels, and its upstream signaling effectors in hippocampal CA1 neurons. The action potential (AP) and voltage-gated potassium currents were determined by using whole-cell patch-clamp. Insulin and CORT improved the neuronal excitability. Independent effects existed in transient potassium channel (IA) and delay rectifier potassium channel (IK). The inhibition of potassium currents, IA in our experiment, could increase neuronal excitability. CORT led to the excitotoxicity of hippocampal neurons via phosphatidylinositol 3 kinase (PI3K)-mediated insulin-signaling pathway. Therefore, the stimulation of excessive CORT induces excitotoxicity of hippocampal neurons and sensitivity of potassium channels via PI3K-mediated insulin-signaling pathway, which indicates one possible way of depression treatment.
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References
Aurand J-M et al (2016) Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway. BIO Web of Conferences 7:04009. https://doi.org/10.1051/bioconf/20160704009
Brown ES, Varghese FP, McEwen BS (2004) Association of depression with medical illness: does cortisol play a role? Biol Psychiatry 55:1–9. https://doi.org/10.1016/s0006-3223(03)00473-6
Buhl ES et al (2010) Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats. Am J Phys Endocrinol Metab 298:E920–E929. https://doi.org/10.1152/ajpendo.00606.2009
Cai S, Huang S, Hao W (2015) New hypothesis and treatment targets of depression: an integrated view of key findings. Neurosci Bull 31:61–74. https://doi.org/10.1007/s12264-014-1486-4
Chen T, Yang J, Ren G, Yang Z, Zhang T (2013) Multi-walled carbon nanotube increases the excitability of hippocampal CA1 neurons through inhibition of potassium channels in rat's brain slices. Toxicol Lett 217:121–128. https://doi.org/10.1016/j.toxlet.2012.12.013
Chen L, Dai J, Wang Z, Zhang H, Huang Y, Zhao Y (2014) Ginseng Total Saponins reverse corticosterone-induced changes in depression-like behavior and hippocampal plasticity-related proteins by interfering with GSK-3 beta -CREB signaling pathway Evid Based Complement Alternat Med : eCAM 2014:506735 https://doi.org/10.1155/2014/506735
Chiu SL, Cline HT (2010) Insulin receptor signaling in the development of neuronal structure and function. Neural Dev 5:18. https://doi.org/10.1186/1749-8104-5-7
Chiu SL, Chen CM, Cline HT (2008) Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron 58:708–719. https://doi.org/10.1016/j.neuron.2008.04.014
Dai W, Yang J, Chen T, Yang Z (2014) Protective effects of bexarotene against amyloid-beta25-35-induced dysfunction in hippocampal neurons through the insulin signaling pathway. Neurodegener Dis 14:77–84. https://doi.org/10.1159/000358397
Dobarro M, Orejana L, Aguirre N, Ramirez MJ (2013) Propranolol reduces cognitive deficits, amyloid beta levels, tau phosphorylation and insulin resistance in response to chronic corticosterone administration. Int J Neuropsychopharmacol 16:1351–1360. https://doi.org/10.1017/s1461145712001393
Gold PW, Machado-Vieira R, Pavlatou MG (2015) Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. Neural Plasticity 2015:1–11. https://doi.org/10.1155/2015/581976
Grinevich V, Seeburg PH, Schwarz MK, Jezova D (2012) Homer 1 – a new player linking the hypothalamic-pituitary-adrenal axis activity to depression and anxiety. Endocr Regul 46:153–159. https://doi.org/10.4149/endo_2012_03_153
Johnson SA, Fournier NM, Kalynchuk LE (2006) Effect of different doses of corticosterone on depression-like behavior and HPA axis responses to a novel stressor. Behav Brain Res 168:280–288. https://doi.org/10.1016/j.bbr.2005.11.019
Joseph A, Turrigiano GG (2017) All for one but not one for all: excitatory synaptic scaling and intrinsic excitability are Coregulated by CaMKIV, whereas inhibitory synaptic scaling is under independent control. J Neurosci 37:6778–6785. https://doi.org/10.1523/jneurosci.0618-17.2017
Karst H, Berger S, Turiault M, Tronche F, Schutz G, Joels M (2005) Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone. Proc Natl Acad Sci U S A 102:19204–19207. https://doi.org/10.1073/pnas.0507572102
Kinlein SA, Shahanoor Z, Romeo RD, Karatsoreos IN (2017) Chronic corticosterone treatment during adolescence has significant effects on metabolism and skeletal development in male C57BL6/N mice. Endocrinology 158:2239–2254. https://doi.org/10.1210/en.2017-00208
Kudryashova IV (2015) Neurodegenerative changes in depression: excitotoxicity or a deficit of trophic factors? Neurochem J 9:1–7. https://doi.org/10.1134/s1819712415010043
Larimore J et al (2017) Dysbindin deficiency modifies the expression of GABA neuron and ion permeation transcripts in the developing Hippocampus. Front Genet 8:14. https://doi.org/10.3389/fgene.2017.00028
Lee B, Sur B, Shim I, Lee H, Hahm DH (2015) Angelica gigas ameliorate depression-like symptoms in rats following chronic corticosterone injection. BMC Complement Altern Med 15:210. https://doi.org/10.1186/s12906-015-0746-9
Liu DH et al (2014) Voltage dependent Potassium Channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction. PLoS One 9:12. https://doi.org/10.1371/journal.pone.0086109
Lucassen PJ et al (2014) Neuropathology of stress. Acta Neuropathol 127:109–135. https://doi.org/10.1007/s00401-013-1223-5
Murray F, Smith DW, Hutson PH (2008) Chronic low dose corticosterone exposure decreased hippocampal cell proliferation, volume and induced anxiety and depression like behaviours in mice. Eur J Pharmacol 583:115–127. https://doi.org/10.1016/j.ejphar.2008.01.014
Osmanovic J, Plaschke K, Salkovic-Petrisic M, Gruenblatt E, Riederer P, Hoyer S (2010) Chronic exogenous corticosterone administration generates an insulin-resistant brain state in rats stress-the international. Journal on the Biology of Stress 13:123–131. https://doi.org/10.3109/10253890903080379
Piroli GG, Grillo CA, Reznikov LR, Adams S, McEwen BS, Charron MJ, Reagan LP (2007) Corticosterone impairs insulin-stimulated translocation of GLUT4 in the rat hippocampus. Neuroendocrinology 85:71–80. https://doi.org/10.1159/000101694
Russell AL, Tasker JG, Lucion AB, Fiedler J, Munhoz CD, Wu TJ, Deak T (2018) Factors promoting vulnerability to dysregulated stress reactivity and stress-related disease. J Neuroendocrinol:e12641. https://doi.org/10.1111/jne.12641
Schroder W, Hinterkeuser S, Seifert G, Schramm J, Jabs R, Wilkin GP, Steinhauser C (2000) Functional and molecular properties of human astrocytes in acute hippocampal slices obtained from patients with temporal lobe epilepsy. Epilepsia 41:S181–S184. https://doi.org/10.1111/j.1528-1157.2000.tb01578.x
Scott LV, Dinan TG (1998) Vasopressin and the regulation of hypothalamic-pituitary-adrenal axis function: implications for the pathophysiology of depression. Life Sci 62:1985–1998
Solas M, Gerenu G, Gil-Bea FJ, Ramirez MJ (2013) Mineralocorticoid receptor activation induces insulin resistance through c-Jun N-terminal kinases in response to chronic corticosterone: cognitive implications. J Neuroendocrinol 25:350–356. https://doi.org/10.1111/jne.12006
Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP (2008) Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci 11:309–317. https://doi.org/10.1038/nn2055
Teramoto N (2006) Physiological roles of ATP-sensitive K+ channels in smooth muscle. J Physiol 572:617–624. https://doi.org/10.1113/jphysiol.2006.105973
Ulloa JL et al (2010) Comparison of the antidepressant sertraline on differential depression-like behaviors elicited by restraint stress and repeated corticosterone administration. Pharmacol Biochem Behav 97:213–221. https://doi.org/10.1016/j.pbb.2010.08.001
Wieczorek L, Fish EW, O'Leary-Moore SK, Parnell SE, Sulik KK (2015) Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice. Alcohol 49:207–217. https://doi.org/10.1016/j.alcohol.2015.01.005
Xiao X, Zhang H, Wang H, Li Q, Zhang T (2017) Neuroprotective effect of amantadine on corticosterone-induced abnormal glutamatergic synaptic transmission of CA3-CA1 pathway in rat's hippocampal slices 71 https://doi.org/10.1002/syn.22010
Xu P, Xu J, Li Z, Yang Z (2012) Expression of TRPC6 in renal cortex and hippocampus of mouse during postnatal development. PLoS One 7:e38503. https://doi.org/10.1371/journal.pone.0038503
Yao JJ, Gao XF, Chow CW, Zhan XQ, Hu CL, Mei YA (2012) Neuritin activates insulin receptor pathway to up-regulate Kv4.2-mediated transient outward K+ current in rat cerebellar granule neurons. J Biol Chem 287:41534–41545. https://doi.org/10.1074/jbc.M112.390260
Yao JJ, Sun J, Zhao QR, Wang CY, Mei YA (2013) Neuregulin-1/ErbB4 signaling regulates Kv4.2-mediated transient outward K+ current through the Akt/mTOR pathway. Am J Physiol Cell Physiol 305:C197–C206. https://doi.org/10.1152/ajpcell.00041.2013
Yasui S et al (2008) Insulin activates ATP-sensitive potassium channels via phosphatidylinositol 3-kinase in cultured vascular smooth muscle cells. J Vasc Res 45:233–243. https://doi.org/10.1159/000112545
Yin H, Wang H, Zhang H, Gao N, Zhang T, Yang Z (2017) Resveratrol attenuates Aβ-induced early hippocampal neuron excitability impairment via recovery of function of potassium channels. Neurotox Res. https://doi.org/10.1007/s12640-017-9726-9
Zhang L, McBain CJ (1995) Potassium conductances underlying repolarization and after-hyperpolarization in rat CA1 hippocampal interneurones. J Physiol 488(Pt 3):661–672
Acknowledgements
This study was supported by grants from the National Natural Science Foundation of China (81571804, 81771979).
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Zhuo Yang, Qingqing Xia and Hui Wang conceived the study and designed the experiments. Qingqing Xia performed all experiments and data analysis, wrote the manuscript and generated the figures. Hongqiang Yin provided the guidance of technique and data analysis. All authors have read and approved the manuscript.
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All animal experiments were approved by the Animal Research Ethics Committee, School of Medicine, Nankai University and were performed in accordance with the Animal Management Rules of the Ministry of Health of the People’s Republic of China.
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Xia, Q., Wang, H., Yin, H. et al. Excessive corticosterone induces excitotoxicity of hippocampal neurons and sensitivity of potassium channels via insulin-signaling pathway. Metab Brain Dis 34, 119–128 (2019). https://doi.org/10.1007/s11011-018-0326-z
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DOI: https://doi.org/10.1007/s11011-018-0326-z