Neuroprotective Action of FK-506 (tacrolimus) After Seizures Induced with Pilocarpine: Quantitative and Topographic Elemental Analysis of Brain Tissue

Overview

Journal J Biol Inorg Chem

Publisher Springer

Specialty Biochemistry

Date 2009 Oct 29

PMID 19862562

Citations 16

Authors

Joanna Chwiej

Krzysztof Janeczko

Marianna Marciszko

Mateusz Czyzycki

Karen Rickers

Zuzanna Setkowicz

Affiliations

Soon will be listed here.

Abstract

In the present work, X-ray fluorescence microscopy with a synchrotron source for the exciting radiation was applied for topographic and quantitative elemental analysis of rat brain tissue in pilocarpine-induced epilepsy and neuroprotection with FK-506. The mass per unit area of the elements P, S, Cl, K, Ca, Fe, Cu, Zn, Se, Br, and Rb was determined in four fields of the hippocampal formation (sectors 1 and 3 of Ammon's horn-CA1, CA3; dentate gyrus; hilus of dentate gyrus) and the parietal cortex. The results obtained for epileptic rats treated with FK-506 (SNF) were compared with data obtained previously for epileptic rats (SNS) and a control group. Many statistically significant differences in elemental composition were observed between the SNF and SNS groups. Higher mass per unit area of P was noticed in CA1 and CA3 regions of the hippocampus of SNF rats in comparison with SNS rats. A similar relation was observed for K in all five brain areas analyzed. Also, Fe in CA3 and dentate gyrus, Cu in the parietal cortex, and Zn in CA3 and in the cortex were present at a higher level in the SNF group in comparison with the SNS group. The findings obtained in the present study suggest that the neuroprotective action of FK-506 in epileptic rat brain may involve not only the inhibition of calcineurin but also blockade of the K(+) channels.

Citing Articles

A review of the "metallome" within neurons and glia, as revealed by elemental mapping of brain tissue.

Ellison G, Hollings A, Hackett M BBA Adv. 2023; 2:100038.

PMID: 37082604 PMC: 10074908. DOI: 10.1016/j.bbadva.2021.100038.

Immunosuppressant Tacrolimus Treatment Delays Acute Seizure Occurrence, Reduces Elevated Oxidative Stress, and Reverses PGF2α Burst in the Brain of PTZ-Treated Rats.

Pazarlar B, Egilmez C, Erdogan M, Erbas O Neurochem Res. 2023; 48(6):1971-1980.

PMID: 36780043 DOI: 10.1007/s11064-023-03885-0.

Perspectives on the Molecular Mediators of Oxidative Stress and Antioxidant Strategies in the Context of Neuroprotection and Neurolongevity: An Extensive Review.

Shohag S, Akhter S, Islam S, Sarker T, Sifat M, Rahman M Oxid Med Cell Longev. 2022; 2022:7743705.

PMID: 36062188 PMC: 9439934. DOI: 10.1155/2022/7743705.

Neuroinflammation: A Signature or a Cause of Epilepsy?.

Pracucci E, Pillai V, Lamers D, Parra R, Landi S Int J Mol Sci. 2021; 22(13).

PMID: 34209535 PMC: 8267969. DOI: 10.3390/ijms22136981.

Sample preparation with sucrose cryoprotection dramatically alters Zn distribution in the rodent hippocampus, as revealed by elemental mapping.

Pushie M, Hollings A, Reinhardt J, Webb S, Lam V, Takechi R J Anal At Spectrom. 2021; 35(11):2498-2508.

PMID: 33795908 PMC: 8009441. DOI: 10.1039/d0ja00323a.

References

Hemenway C, Heitman J . Calcineurin. Structure, function, and inhibition. Cell Biochem Biophys. 1999; 30(1):115-51. DOI: 10.1007/BF02737887. View

Toung T, Bhardwaj A, Dawson V, Dawson T, Traystman R, Hurn P . Neuroprotective FK506 does not alter in vivo nitric oxide production during ischemia and early reperfusion in rats. Stroke. 1999; 30(6):1279-85. DOI: 10.1161/01.str.30.6.1279. View

Setkowicz Z, Ciarach M, Guzik R, Janeczko K . Different effects of neuroprotectants FK-506 and cyclosporin A on susceptibility to pilocarpine-induced seizures in rats with brain injured at different developmental stages. Epilepsy Res. 2004; 61(1-3):63-72. DOI: 10.1016/j.eplepsyres.2004.06.001. View

Arii T, Kamiya T, Arii K, Ueda M, Nito C, Katsura K . Neuroprotective effect of immunosuppressant FK506 in transient focal ischemia in rat: therapeutic time window for FK506 in transient focal ischemia. Neurol Res. 2001; 23(7):755-60. DOI: 10.1179/016164101101199135. View

Lieberman D, Mody I . Regulation of NMDA channel function by endogenous Ca(2+)-dependent phosphatase. Nature. 1994; 369(6477):235-9. DOI: 10.1038/369235a0. View

Klee C, Ren H, Wang X . Regulation of the calmodulin-stimulated protein phosphatase, calcineurin. J Biol Chem. 1998; 273(22):13367-70. DOI: 10.1074/jbc.273.22.13367. View

Butcher S, Henshall D, Teramura Y, Iwasaki K, Sharkey J . Neuroprotective actions of FK506 in experimental stroke: in vivo evidence against an antiexcitotoxic mechanism. J Neurosci. 1997; 17(18):6939-46. PMC: 6573264. View

Liu J, Farmer Jr J, Lane W, Friedman J, Weissman I, Schreiber S . Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991; 66(4):807-15. DOI: 10.1016/0092-8674(91)90124-h. View

Griffith J, Kim J, Kim E, Sintchak M, Thomson J, Fitzgibbon M . X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Cell. 1995; 82(3):507-22. DOI: 10.1016/0092-8674(95)90439-5. View

10.

Setkowicz Z, Ciarach M . Neuroprotectants FK-506 and cyclosporin A ameliorate the course of pilocarpine-induced seizures. Epilepsy Res. 2006; 73(2):151-5. DOI: 10.1016/j.eplepsyres.2006.09.001. View

11.

Bartynski W, Zeigler Z, SPEARMAN M, Lin L, Shadduck R, Lister J . Etiology of cortical and white matter lesions in cyclosporin-A and FK-506 neurotoxicity. AJNR Am J Neuroradiol. 2001; 22(10):1901-14. PMC: 7973826. View

12.

Fahrni C . Biological applications of X-ray fluorescence microscopy: exploring the subcellular topography and speciation of transition metals. Curr Opin Chem Biol. 2007; 11(2):121-7. DOI: 10.1016/j.cbpa.2007.02.039. View

13.

Furuichi Y, Katsuta K, Maeda M, Ueyama N, Moriguchi A, Matsuoka N . Neuroprotective action of tacrolimus (FK506) in focal and global cerebral ischemia in rodents: dose dependency, therapeutic time window and long-term efficacy. Brain Res. 2003; 965(1-2):137-45. DOI: 10.1016/s0006-8993(02)04151-3. View

14.

Uchino H, Minamikawa-Tachino R, Kristian T, Perkins G, Narazaki M, Siesjo B . Differential neuroprotection by cyclosporin A and FK506 following ischemia corresponds with differing abilities to inhibit calcineurin and the mitochondrial permeability transition. Neurobiol Dis. 2002; 10(3):219-33. DOI: 10.1006/nbdi.2002.0514. View

15.

Turski L, Ikonomidou C, Turski W, Bortolotto Z, Cavalheiro E . Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. Synapse. 1989; 3(2):154-71. DOI: 10.1002/syn.890030207. View

16.

Paunesku T, Vogt S, Maser J, Lai B, Woloschak G . X-ray fluorescence microprobe imaging in biology and medicine. J Cell Biochem. 2006; 99(6):1489-502. DOI: 10.1002/jcb.21047. View

17.

Covolan L, Mello L . Temporal profile of neuronal injury following pilocarpine or kainic acid-induced status epilepticus. Epilepsy Res. 2000; 39(2):133-52. DOI: 10.1016/s0920-1211(99)00119-9. View

18.

Turski W, Cavalheiro E, Bortolotto Z, Mello L, Schwarz M, Turski L . Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. Brain Res. 1984; 321(2):237-53. DOI: 10.1016/0006-8993(84)90177-x. View

19.

Furuichi Y, Maeda M, Moriguchi A, Sawamoto T, Kawamura A, Matsuoka N . Tacrolimus, a potential neuroprotective agent, ameliorates ischemic brain damage and neurologic deficits after focal cerebral ischemia in nonhuman primates. J Cereb Blood Flow Metab. 2003; 23(10):1183-94. DOI: 10.1097/01.WCB.0000088761.02615.EB. View

20.

Yakel J . Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription. Trends Pharmacol Sci. 1997; 18(4):124-34. DOI: 10.1016/s0165-6147(97)01046-8. View