Monocyte chemoattractant protein-1 affects migration of hippocampal neural progenitors following status epilepticus in rats

Journal of Neuroinflammation

Yung-Yang Lin²  Chien-Chen Chou¹  Yi-Jhan Tseng¹  Ming-Tsong Lai¹  Yu-Wen Hung¹ 

[1] Laboratory of Neurophysiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd, Taipei, 112, Taiwan;Department of Neurology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd, Taipei, 112, Taiwan

关键词: Rats;    Pilocarpine-induced status epilepticus;    Neuronal progenitor migration;    Neuroinflammation;    Monocyte chemoattractant protein-1 (MCP-1);    Epileptogenesis;    Dentate gyrus;    Chemokine (C-C motif) receptor 2 (CCR2);   

Others  :  1160061
DOI  :  10.1186/1742-2094-10-11

 received in 2012-01-19, accepted in 2013-01-07,  发布年份 2013

【 摘 要 】

Background

Epilepsy is a common brain disorder characterized by a chronic predisposition to generate spontaneous seizures. The mechanisms for epilepsy formation remain unknown. A growing body of evidence suggests the involvement of inflammatory processes in epileptogenesis. In the present study, we investigated the involvement of monocyte chemoattractant protein-1 (MCP-1) in aberrant migration of hippocampal progenitors in rats after the insult of status epilepticus (SE).

Methods

SE was induced with pilocarpine in Sprague–Dawley rats. Transcriptional expression of MCP-1 in the dentate gyrus (DG) was measured using quantitative real-time PCR. From 1 to 28 days after SE, the temporal profiles of MCP-1 protein expression in DG were evaluated using enzyme-linked immunosorbent assay. Chemokine (C-C motif) receptor 2 (CCR2) expression in doublecortin-positive neuronal progenitors was examined using double-labeling immunohistochemistry. The involvement of MCP-1/CCR2 signaling in aberrant neuronal progenitor migration in the epileptic hippocampus was assessed in the SE rats using a CCR2 antagonist, RS102895, and the ectopic migration of neuronal progenitors was determined using Prox1/doublecortin double immunostaining.

Results

After SE, MCP-1 gene was significantly upregulated and its corresponding protein expression in the DG was significantly increased on days 1 and 3. Some hilar ectopic progenitor cells of SE rats expressed the MCP-1 receptor, CCR2. Notably, the ectopic migration of neuronal progenitors into hilus was attenuated by a blockade of the MCP-1/CCR2 interaction with a selective CCR2 inhibitor, RS102895.

Conclusions

An increase in dentate MCP-1 is associated with seizure-induced aberrant migration of neuronal progenitors through the interaction with CCR2. The upregulation of MCP-1 after an insult of SE may play a role in the generation of epilepsy.

【 授权许可】

   
2013 Hung et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Spencer SS: When should temporal-lobe epilepsy be treated surgically? Lancet Neurol 2002, 1:375-382.
• [2]Buckmaster PS: Laboratory animal models of temporal lobe epilepsy. Comp Med 2004, 54:473-485.
• [3]Dalby NO, Mody I: The process of epileptogenesis: a pathophysiological approach. Curr Opin Neurol 2001, 14:187-192.
• [4]Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH: Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 1997, 17:3727-3738.
• [5]Vezzani A, Granata T: Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 2005, 46:1724-1743.
• [6]Chang BS, Lowenstein DH: Epilepsy. N Engl J Med 2003, 349:1257-1266.
• [7]Turrin NP, Rivest S: Innate immune reaction in response to seizures: implications for the neuropathology associated with epilepsy. Neurobiol Dis 2004, 16:321-334.
• [8]Vezzani A, French J, Bartfai T, Baram TZ: The role of inflammation in epilepsy. Nat Rev Neurol 2011, 7:31-40.
• [9]Vezzani A, Balosso S, Ravizza T: The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun 2008, 22:797-803.
• [10]Asensio VC, Campbell IL: Chemokines in the CNS: plurifunctional mediators in diverse states. Trends Neurosci 1999, 22:504-512.
• [11]Cartier L, Hartley O, Dubois-Dauphin M, Krause KH: Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 2005, 48:16-42.
• [12]Huang D, Han Y, Rani MR, Glabinski A, Trebst C, Sorensen T, Tani M, Wang J, Chien P, O’Bryan S, Bielecki B, Zhou ZL, Majumder S, Ransohoff RM: Chemokines and chemokine receptors in inflammation of the nervous system: manifold roles and exquisite regulation. Immunol Rev 2000, 177:52-67.
• [13]Miller RJ, Rostene W, Apartis E, Banisadr G, Biber K, Milligan ED, White FA, Zhang J: Chemokine action in the nervous system. J Neurosci 2008, 28:11792-11795.
• [14]Choi J, Nordli DR Jr, Alden TD, DiPatri A Jr, Laux L, Kelley K, Rosenow J, Schuele SU, Rajaram V, Koh S: Cellular injury and neuroinflammation in children with chronic intractable epilepsy. J Neuroinflammation 2009, 6:38. BioMed Central Full Text
• [15]van Gassen KL, de Wit M, Koerkamp MJ, Rensen MG, van Rijen PC, Holstege FC, Lindhout D, de Graan PN: Possible role of the innate immunity in temporal lobe epilepsy. Epilepsia 2008, 49:1055-1065.
• [16]Wu Y, Wang X, Mo X, Xi Z, Xiao F, Li J, Zhu X, Luan G, Wang Y, Li Y, Zhang J: Expression of monocyte chemoattractant protein-1 in brain tissue of patients with intractable epilepsy. Clin Neuropathol 2008, 27:55-63.
• [17]Foresti ML, Arisi GM, Katki K, Montanez A, Sanchez RM, Shapiro LA: Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following pilocarpine-induced status epilepticus. J Neuroinflammation 2009, 6:40. BioMed Central Full Text
• [18]Manley NC, Bertrand AA, Kinney KS, Hing TC, Sapolsky RM: Characterization of monocyte chemoattractant protein-1 expression following a kainate model of status epilepticus. Brain Res 2007, 1182:138-143.
• [19]Stamatovic SM, Shakui P, Keep RF, Moore BB, Kunkel SL, Van Rooijen N, Andjelkovic AV: Monocyte chemoattractant protein-1 regulation of blood–brain barrier permeability. J Cereb Blood Flow Metab 2005, 25:593-606.
• [20]Yadav A, Saini V, Arora S: MCP-1: chemoattractant with a role beyond immunity: a review. Clin Chim Acta 2010, 411:1570-1579.
• [21]Iyer AM, Zurolo E, Boer K, Baayen JC, Giangaspero F, Arcella A, Di Gennaro GC, Esposito V, Spliet WG, van Rijen PC, Troost D, Gorter JA, Aronica E: Tissue plasminogen activator and urokinase plasminogen activator in human epileptogenic pathologies. Neuroscience 2010, 167:929-945.
• [22]Widera D, Holtkamp W, Entschladen F, Niggemann B, Zanker K, Kaltschmidt B, Kaltschmidt C: MCP-1 induces migration of adult neural stem cells. Eur J Cell Biol 2004, 83:381-387.
• [23]Yan YP, Sailor KA, Lang BT, Park SW, Vemuganti R, Dempsey RJ: Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia. J Cereb Blood Flow Metab 2007, 27:1213-1224.
• [24]Belmadani A, Tran PB, Ren D, Miller RJ: Chemokines regulate the migration of neural progenitors to sites of neuroinflammation. J Neurosci 2006, 26:3182-3191.
• [25]Overstreet-Wadiche LS, Bromberg DA, Bensen AL, Westbrook GL: Seizures accelerate functional integration of adult-generated granule cells. J Neurosci 2006, 26:4095-4103.
• [26]Walter C, Murphy BL, Pun RY, Spieles-Engemann AL, Danzer SC: Pilocarpine-induced seizures cause selective time-dependent changes to adult-generated hippocampal dentate granule cells. J Neurosci 2007, 27:7541-7552.
• [27]Parent JM: Adult neurogenesis in the intact and epileptic dentate gyrus. Prog Brain Res 2007, 163:529-540.
• [28]Zheng Y, Moussally J, Cash SS, Karnam HB, Cole AJ: Intravenous levetiracetam in the rat pilocarpine-induced status epilepticus model: behavioral, physiological and histological studies. Neuropharmacology 2010, 58:793-798.
• [29]Elmarakby AA, Quigley JE, Olearczyk JJ, Sridhar A, Cook AK, Inscho EW, Pollock DM, Imig JD: Chemokine receptor 2b inhibition provides renal protection in angiotensin II - salt hypertension. Hypertension 2007, 50:1069-1076.
• [30]Mirzadegan T, Diehl F, Ebi B, Bhakta S, Polsky I, McCarley D, Mulkins M, Weatherhead GS, Lapierre JM, Dankwardt J, Jr Morgans D, Wilhelm R, Jarnagin K: Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle. J Biol Chem 2000, 275:25562-25571.
• [31]Hagihara H, Toyama K, Yamasaki N, Miyakawa T: Dissection of hippocampal dentate gyrus from adult mouse. J Vis Exp 2009, 33:e1543.
• [32]Holland PM, Abramson RD, Watson R, Gelfand DH: Detection of specific polymerase chain reaction product by utilizing the 5′–3′exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci U S A 1991, 88:7276-7280.
• [33]Kralic JE, Ledergerber DA, Fritschy JM: Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures. Eur J Neurosci 2005, 22:1916-1927.
• [34]West MJ, Slomianka L, Gundersen HJ: Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator. Anat Rec 1991, 231:482-497.
• [35]McCloskey DP, Hintz TM, Pierce JP, Scharfman HE: Stereological methods reveal the robust size and stability of ectopic hilar granule cells after pilocarpine-induced status epilepticus in the adult rat. Eur J Neurosci 2006, 24:2203-2210.
• [36]West MJ: New stereological methods for counting neurons. Neurobiol Aging 1993, 14:275-285.
• [37]Mouton PR: Principles and practices of unbiased stereology: an introduction for bioscientists. Baltimore: Johns Hopkins University Press; 2002.
• [38]Wong-Goodrich SJ, Mellott TJ, Glenn MJ, Blusztajn JK, Williams CL: Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus. Neurobiol Dis 2008, 30:255-269.
• [39]Scharfman HE: Functional implications of seizure-induced neurogenesis. Adv Exp Med Biol 2004, 548:192-212.
• [40]Scharfman HE, Goodman JH, Sollas AL: Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells: functional implications of seizure-induced neurogenesis. J Neurosci 2000, 20:6144-6158.
• [41]Gong C, Wang TW, Huang HS, Parent JM: Reelin regulates neuronal progenitor migration in intact and epileptic hippocampus. J Neurosci 2007, 27:1803-1811.
• [42]Parent JM, Elliott RC, Pleasure SJ, Barbaro NM, Lowenstein DH: Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Ann Neurol 2006, 59:81-91.
• [43]Sheehan JJ, Zhou C, Gravanis I, Rogove AD, Wu YP, Bogenhagen DF, Tsirka SE: Proteolytic activation of monocyte chemoattractant protein-1 by plasmin underlies excitotoxic neurodegeneration in mice. J Neurosci 2007, 27:1738-1745.
• [44]Kalehua AN, Nagel JE, Whelchel LM, Gides JJ, Pyle RS, Smith RJ, Kusiak JW, Taub DD: Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are involved in both excitotoxin-induced neurodegeneration and regeneration. Exp Cell Res 2004, 297:197-211.
• [45]Tran PB, Banisadr G, Ren D, Chenn A, Miller RJ: Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain. J Comp Neurol 2007, 500:1007-1033.
• [46]Hartman NW, Carpentino JE, LaMonica K, Mor DE, Naegele JR, Grabel L: CXCL12-mediated guidance of migrating embryonic stem cell-derived neural progenitors transplanted into the hippocampus. PLoS One 2010, 5:e15856.