- Short communication
Erythropoietin affects GABAergic transmission in hippocampal neurons in vitro
Cellular & Molecular Biology Letters volume 13, pages 649–655 (2008)
Erythropoietin is a potent regulator of erythropoiesis. It acts via the specific membrane receptor (EpoR). Erythropoietin is also known to be present in the central nervous system, and its concentration and the expression of EpoR change during development, which raises the possibility that this modulator might be involved in the regulation of neuronal functions in the developing brain. The GABAergic system undergoes profound changes during development and is particularly susceptible to modulation by endogenous factors. Therefore, we decided to investigate the impact of Epo on GABAergic transmission in hippocampal neurons developing in vitro. An analysis of miniature IPSCs (mIPSCs) revealed that a long-term treatment with Epo (48 or 72 h) resulted in a major acceleration of the decaying phase of these currents while the amplitude and current frequency remained unchanged. Interestingly, this effect was restricted to the youngest considered age group (6-8 DIV), indicating that Epomediated modulation of mIPSCs depends on the developmental stage of the neurons. We conclude that Epo may exert a modulatory action on GABAergic transmission in developing neural networks.
gamma aminobutyric acid
miniature inhibitory postsynaptic current
Genc, S., Koroglu, T.F. and Genc, K. Erythropoietin and the nervous system. Brain Res. 1000 (2004) 19–31.
Digicaylioglu, M., Bichet, S., Marti, H.H., Wenger, R.H., Rivas, L.A., Bauer, C. and Gassmann, M. Localization of specific erythropoietin binding sites in defined areas of the mouse brain. Proc. Natl. Acad. Sci. USA 92 (1995) 3717–3720.
Masuda, S., Nagao, M., Takahata, K., Konishi, Y., Gallyas, F. Jr., Tabira, T. and Sasaki, R. Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. J. Biol. Chem. 268 (1993) 11208–11216.
Tan, C.C., Eckardt, K.U., Firth, J.D. and Ratcliffe, P.J. Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia. Am. J. Physiol. 263 (1992) F474–481.
Brines, M.L., Ghezzi, P., Keenan, S., Agnello, D., de Lanerolle, N.C., Cerami, C., Itri, L.M. and Cerami, A. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc. Natl. Acad. Sci. USA 97 (2000) 10526–10531.
Kumral, A., Ozer, E., Yilmaz, O., Akhisaroglu, M., Gokmen, N., Duman, N., Ulukus, C., Genc, S. and Ozkan, H. Neuroprotective effect of erythropoietin on hypoxic-ischemic brain injury in neonatal rats. Biol. Neonat. 83 (2003) 224–228.
Buemi, M., Cavallaro, E., Floccari, F., Sturiale, A., Aloisi, C., Trimarchi, M., Grasso, G., Corica, F. and Frisina, N. Erythropoietin and the brain: from neurodevelopment to neuroprotection. Clin. Sci. (Lond) 103 (2002) 275–282.
Zhang, F., Signore, A.P., Zhou, Z., Wang, S., Cao, G. and Chen, J. Erythropoietin protects CA1 neurons against global cerebral ischemia in rat: potential signaling mechanisms. J. Neurosci. Res. 83 (2006) 1241–1251.
Yang, J., Huang, Y., Yu, X., Sun, H., Li, Y. and Deng, Y. Erythropoietin preconditioning suppresses neuronal death following status epilepticus in rats. Acta Neurobiol. Exp. (Wars) 67 (2007) 141–148.
Ransome, M.I. and Turnley, A.M. Systemically delivered Erythropoietin transiently enhances adult hippocampal neurogenesis. J. Neurochem. 102 (2007) 1953–1965.
Dame, C., Bartmann, P., Wolber, E., Fahnenstich, H., Hofmann, D. and Fandrey, J. Erythropoietin gene expression in different areas of the developing human central nervous system. Brain Res. Dev. Brain Res. 125 (2000) 69–74.
Juul, S. Erythropoietin in the central nervous system, and its use to prevent hypoxic-ischemic brain damage. Acta Paediatr. Suppl. 91 (2002) 36–42.
Juul, S.E., Yachnis, A.T., Rojiani, A.M. and Christensen, R.D. Immunohistochemical localization of erythropoietin and its receptor in the developing human brain. Pediatr. Dev. Pathol. 2 (1999) 148–158.
Hollrigel, G.S. and Soltesz, I. Slow kinetics of miniature IPSCs during early postnatal development in granule cells of the dentate gyrus. J. Neurosci. 17 (1997) 5119–5128.
Andjus, P.R., Stevic-Marinkovic, Z. and Cherubini, E. Immunoglobulins from motoneurone disease patients enhance glutamate release from rat hippocampal neurones in culture. J. Physiol. 504 (1997) 103–112.
Pytel, M., Wojtowicz, T., Mercik, K., Sarto-Jackson, I., Sieghart, W., Ikonomidou, C. and Mozrzymas, J.W. 17 beta-estradiol modulates GABAergic synaptic transmission and tonic currents during development in vitro. Neuropharmacology 52 (2007) 1342–1353.
Clements, J.D. Transmitter timecourse in the synaptic cleft: its role in central synaptic function. Trends. Neurosci. 19 (1996) 163–171.
Mozrzymas, J.W. Dynamism of GABA(A) receptor activation shapes the “personality” of inhibitory synapses. Neuropharmacology 47 (2004) 945–960.
Cherubini, E., Gaiarsa, J.L. and Ben-Ari, Y. GABA: an excitatory transmitter in early postnatal life. Trends. Neurosci. 14 (1991) 515–519.
About this article
Cite this article
Wójtowicz, T., Mozrzymas, J.W. Erythropoietin affects GABAergic transmission in hippocampal neurons in vitro . Cell Mol Biol Lett 13, 649–655 (2008). https://doi.org/10.2478/s11658-008-0029-2
- GABAA receptors
- Miniature post synaptic current mIPSC
- Neuronal culture