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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Mini-Review Article

Potential Cytokine Biomarkers in Intellectual Disability

Author(s): Yousra Benmakhlouf, Zeineb Zian*, Naima G. Nourouti, Amina Barakat and Mohcine B. Mechita

Volume 21, Issue 4, 2021

Published on: 27 June, 2020

Page: [569 - 576] Pages: 8

DOI: 10.2174/1871530320666200628024944

Price: $65

Abstract

Intellectual disability (ID), previously called mental retardation, is the most common neurodevelopmental disorder characterized by life-long intellectual and adaptive functioning impairments that have an impact on individuals, families, and society. Its prevalence is estimated to 3% of the general population and its etiology is still insufficiently understood. Besides the involvement of genetic and environmental factors, immunological dysfunctions have been also suggested to contribute to the pathophysiology of ID. Over the years, immune biomarkers related to ID have gained significant attention and researchers have begun to look at possible cytokine profiles in individuals suffered from this disorder. In fact, in addition to playing crucial physiological roles in the majority of normal neurodevelopmental processes, cytokines exert an important role in neuroinflammation under pathological conditions, and interactions between the immune system and central nervous system have long been under investigation. Cytokine levels imbalance has been reported associated with some behavioral characteristics and the onset of some syndromic forms of ID.

In this review, we will focus on immunological biomarkers, especially the cytokine profiles that have been identified in people with ID. Thus, data reported and discussed in the present paper may provide additional information to start further studies and to plan strategies for early identification and managing of ID.

Keywords: Chemokines, cytokines, intellectual disability, mental retardation, neurodevelopmental disorder, neuroinflammation.

Graphical Abstract

[1]
Aureli, A.; Sebastiani, P.; Del Beato, T.; Marimpietri, A.E.; Graziani, A. Involvement of IL-6 and IL-1 receptor antagonist on intellectual disability. Immunol. Lett., 2014, 162(1), 124-131.
[http://dx.doi.org/10.1016/j.imlet.2014.08.003]] [PMID: 25124963]
[2]
Katz, G.; Lazcano-Ponce, E. Intellectual disability: definition, etiological factors, classification, diagnosis, treatment and prognosis. Salud Publica Mex., 2008, 50(Suppl. 2), s132-s141.
[http://dx.doi.org/10.1590/S0036-36342008000800005] [PMID: 18470340]
[3]
Belkady, B.; Elkhattabi, L.; Elkarhat, Z.; Zarouf, L.; Razoki, L.; Aboulfaraj, J.; Nassereddine, S.; Cadi, R.; Rouba, H.; Barakat, A. Chromosomal abnormalities in patients with intellectual disability: a 21-year retrospective study. Hum. Hered., 2018, 83(5), 274-282.
[http://dx.doi.org/10.1159/000499710] [PMID: 31064002]
[4]
Aureli, A.; Sebastiani, P.; Del Beato, T.; Colanardi, A.; Grannonico, M.; Elvira Marimpietri, A.; Sechi, E.; Di Loreto, S. IL-1β polymorphisms and its interaction with Nrg-1 on the risk of intellectual disability. J. Psychol. Cogn., 2018, 3(3), 54-60.
[http://dx.doi.org/10.35841/psychology-cognition.3.54-60]
[5]
Jin, P.; Warren, S.T. Understanding the molecular basis of fragile X syndrome. Hum. Mol. Genet., 2000, 9(6), 901-908.
[http://dx.doi.org/10.1093/hmg/9.6.901]
[6]
Ashwood, P.; Nguyen, D.V.; Hessl, D.; Hagerman, R.J.; Tassone, F. Plasma cytokine profiles in Fragile X subjects: is there a role for cytokines in the pathogenesis? Brain Behav. Immun., 2010, 24(6), 898-902.
[http://dx.doi.org/10.1016/j.bbi.2010.01.008] [PMID: 20102735]
[7]
Pozzi, D.; Menna, E.; Canzi, A.; Desiato, G.; Mantovani, C.; Matteoli, M. The communication between the immune and nervous systems: the role of IL-1β in Synaptopathies. Front. Mol. Neurosci., 2018, 11, 111.
[http://dx.doi.org/10.3389/fnmol.2018.00111] [PMID: 29674955]
[8]
Di Marco, B.; Bonaccorso, C.M.; Aloisi, E.; D’Antoni, S.; Catania, M.V. Neuro-inflammatory mechanisms in developmental disorders associated with intellectual disability and autism spectrum disorder: a neuro-immune perspective. CNS Neurol. Disord. Drug Targets, 2016, 15(4), 448-463.
[http://dx.doi.org/10.2174/1871527315666160321105039] [PMID: 26996174]
[9]
Deverman, B.E.; Patterson, P.H. Cytokines and CNS development. Neuron, 2009, 64(1), 61-78.
[http://dx.doi.org/10.1016/j.neuron.2009.09.002] [PMID: 19840550]
[10]
Di Filippo, M.; Chiasserini, D.; Gardoni, F.; Viviani, B.; Tozzi, A.; Giampà, C.; Costa, C.; Tantucci, M.; Zianni, E.; Boraso, M.; Siliquini, S.; de Iure, A.; Ghiglieri, V.; Colcelli, E.; Baker, D.; Sarchielli, P.; Fusco, F.R.; Di Luca, M.; Calabresi, P. Effects of central and peripheral inflammation on hippocampal synaptic plasticity. Neurobiol. Dis., 2013, 52, 229-236.
[http://dx.doi.org/10.1016/j.nbd.2012.12.009] [PMID: 23295855]
[11]
Di Filippo, M.; Sarchielli, P.; Picconi, B.; Calabresi, P. Neuroinflammation and synaptic plasticity: theoretical basis for a novel, immune-centred, therapeutic approach to neurological disorders. Trends Pharmacol. Sci., 2008, 29(8), 402-412.
[http://dx.doi.org/10.1016/j.tips.2008.06.005] [PMID: 18617277]
[12]
Vezzani, A.; Viviani, B. Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability., Neuropharmacology, 2015, 96(Pt A), 70-82..
[http://dx.doi.org/10.1016/j.neuropharm.2014.10.027] [PMID: 25445483]
[13]
Yaffe, K.; Lindquist, K.; Penninx, B.W.; Simonsick, E.M.; Pahor, M.; Kritchevsky, S.; Launer, L.; Kuller, L.; Rubin, S.; Harris, T. Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology, 2003, 61(1), 76-80.
[http://dx.doi.org/10.1212/01.WNL.0000073620.42047.D7] [PMID: 12847160]
[14]
Engelhart, M.J.; Geerlings, M.I.; Meijer, J.; Kiliaan, A.; Ruitenberg, A.; van Swieten, J.C.; Stijnen, T.; Hofman, A.; Witteman, J.C.; Breteler, M.M. Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch. Neurol., 2004, 61(5), 668-672.
[http://dx.doi.org/10.1001/archneur.61.5.668] [PMID: 15148142]
[15]
Zhuang, L.; Liu, X.; Xu, X.; Yue, C.; Shu, H.; Bai, F.; Yu, H.; Shi, Y.; Zhang, Z. Association of the interleukin 1 beta gene and brain spontaneous activity in amnestic mild cognitive impairment. J. Neuroinflammation, 2012, 9(1), 263.
[http://dx.doi.org/10.1186/1742-2094-9-263] [PMID: 23199001]
[16]
O’Tuathaigh, C.M.P.; Babovic, D.; O’Sullivan, G.J.; Clifford, J.J.; Tighe, O.; Croke, D.T.; Harvey, R.; Waddington, J.L. Phenotypic characterization of spatial cognition and social behavior in mice with ‘knockout’ of the schizophrenia risk gene neuregulin. Neuroscience, 2007, 147(1), 18-27.
[http://dx.doi.org/10.1016/j.neuroscience.2007.03.051] [PMID: 17512671]
[17]
Pinto, J.V.; Passos, I.C.; Librenza-Garcia, D.; Marcon, G.; Schneider, M.A.; Conte, J.H.; da Silva, J.P.A.; Lima, L.P.; Quincozes-Santos, A.; Kauer-Sant Anna, M.; Kapczinski, F. Neuron-glia Interaction as a possible pathophysiological mechanism of bipolar disorder. Curr. Neuropharmacol., 2018, 16(5), 519-532.
[http://dx.doi.org/10.2174/1570159X15666170828170921] [PMID: 28847296]
[18]
Jones, K.A.; Thomsen, C. The role of the innate immune system in psychiatric disorders. Mol. Cell. Neurosci., 2013, 53, 52-62.
[http://dx.doi.org/10.1016/j.mcn.2012.10.002] [PMID: 23064447]
[19]
Shastri, A.; Bonifati, D.M.; Kishore, U. Innate immunity and neuroinflammation. Mediators Inflamm., 2013, 2013342931
[http://dx.doi.org/10.1155/2013/342931] [PMID: 23843682]
[20]
Dinarello, C.A. Historical review of cytokines. Eur. J. Immunol., 2007, 37(Suppl. 1), S34-S45.
[http://dx.doi.org/10.1002/eji.200737772]] [PMID: 17972343]
[21]
Pickering, M.; O’Connor, J.J. Pro-inflammatory cytokines and their effects in the dentate gyrus; . Prog. Brain Res., 2007, 163, 339-354..
[http://dx.doi.org/10.1016/S0079-6123(07)63020-9 ] [PMID: 17765728]
[22]
Viviani, B.; Gardoni, F.; Marinovich, M. Cytokines and neuronal ion channels in health and disease. Int. Rev. Neurobiol., 2007, 82, 247-263.
[http://dx.doi.org/10.1016/S0074-7742(07)82013-7]] [PMID: 17678965]
[23]
Pribiag, H.; Stellwagen, D. Neuroimmune regulation of homeostatic synaptic plasticity. Neuropharmacology, 2014, 78, 13-22.
[http://dx.doi.org/10.1016/j.neuropharm.2013.06.008] [PMID: 23774138]
[24]
Ratnayake, U.; Quinn, T.; Walker, D.W.; Dickinson, H. Cytokines and the neurodevelopmental basis of mental illness. Front. Neurosci., 2013, 7, 180.
[http://dx.doi.org/10.3389/fnins.2013.00180] [PMID: 24146637]
[25]
Sengupta, A.; Das, U.; Manna, K.; Biswas, S.; Datta, S.; Khan, A.; Bhattacharya, T.; Saha, S.; Mitra, T.; Mukherjee, S.; Sadhu, A.; Paul, S.; Ghosh, S.; Sharma, R.D.; De, S. An association study of severity of intellectual disability with peripheral biomarkers of disabled children in a rehabilitation home, Kolkata, India. Sci. Rep., 2019, 9(1), 13652.
[http://dx.doi.org/10.1038/s41598-019-49728-3]]
[26]
Goines, P.E.; Croen, L.A.; Braunschweig, D.; Yoshida, C.K.; Grether, J.; Hansen, R.; Kharrazi, M.; Ashwood, P.; Van de Water, J. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study. Mol. Autism, 2011, 2(1), 13.
[http://dx.doi.org/10.1186/2040-2392-2-13] [PMID: 21810230]
[27]
von Ehrenstein, O.S.; Neta, G.I.; Andrews, W.; Goldenberg, R.; Goepfert, A.; Zhang, J. Child intellectual development in relation to cytokine levels in umbilical cord blood. Am. J. Epidemiol., 2012, 175(11), 1191-1199.
[http://dx.doi.org/10.1093/aje/kwr393] [PMID: 22508393]
[28]
Jones, K.L.; Croen, L.A.; Yoshida, C.K.; Heuer, L.; Hansen, R.; Zerbo, O.; DeLorenze, G.N.; Kharrazi, M.; Yolken, R.; Ashwood, P.; Van de Water, J. Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation. Mol. Psychiatry, 2017, 22(2), 273-279.
[http://dx.doi.org/10.1038/mp.2016.77] [PMID: 27217154]
[29]
Gruol, D.L. IL-6 regulation of synaptic function in the CNS. Neuropharmacology,2015, 96(Pt A), 42-54..
[http://dx.doi.org/10.1016/j.neuropharm.2014.10.023] [PMID: 25445486]
[30]
Zaretsky, M.V.; Alexander, J.M.; Byrd, W.; Bawdon, R.E. Transfer of inflammatory cytokines across the placenta. Obstet. Gynecol., 2004, 103(3), 546-550.
[http://dx.doi.org/10.1097/01.AOG.0000114980.40445.83] [PMID: 14990420]
[31]
Banks, W.A.; Kastin, A.J.; Broadwell, R.D. Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation, 1995, 2(4), 241-248.
[http://dx.doi.org/10.1159/000097202]] [PMID: 8963753]
[32]
Arisi, G.M. Nervous and immune systems signals and connections: cytokines in hippocampus physiology and pathology. Epilepsy Behav., 2014, 38, 43-47.
[http://dx.doi.org/10.1016/j.yebeh.2014.01.017] [PMID: 24534466]
[33]
McAfoose, J.; Baune, B.T. Evidence for a cytokine model of cognitive function. Neurosci. Biobehav. Rev., 2009, 33(3), 355-366.
[http://dx.doi.org/10.1016/j.neubiorev.2008.10.005]
[34]
Yirmiya, R.; Goshen, I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav. Immun., 2011, 25(2), 181-213.
[http://dx.doi.org/10.1016/j.bbi.2010.10.015] [PMID: 20970492]
[35]
Ramaswamy, V.; Horton, J.; Vandermeer, B.; Buscemi, N.; Miller, S.; Yager, J. Systematic review of biomarkers of brain injury in term neonatal encephalopathy. Pediatr. Neurol., 2009, 40(3), 215-226.
[http://dx.doi.org/10.1016/j.pediatrneurol.2008.09.026]
[36]
Wei, H.; Chadman, K.K.; McCloskey, D.P.; Sheikh, A.M.; Malik, M.; Brown, W.T.; Li, X. Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim. Biophys. Acta, 2012, 1822(6), 831-842.
[http://dx.doi.org/10.1016/j.bbadis.2012.01.011] [PMID: 22326556]
[37]
Braida, D.; Sacerdote, P.; Panerai, A.E.; Bianchi, M.; Aloisi, A.M.; Iosuè, S.; Sala, M. Cognitive function in young and adult IL (interleukin)-6 deficient mice. Behav. Brain Res., 2004, 153(2), 423-429.
[http://dx.doi.org/10.1016/j.bbr.2003.12.018] [PMID: 15265638]
[38]
Hryniewicz, A.; Bialuk, I.; Kamiński, K.A.; Winnicka, M.M. Impairment of recognition memory in interleukin-6 knock-out mice. Eur. J. Pharmacol., 2007, 577(1-3), 219-220.
[http://dx.doi.org/10.1016/j.ejphar.2007.08.046] [PMID: 17920057]
[39]
Ashwood, P.; Krakowiak, P.; Hertz-Picciotto, I.; Hansen, R.; Pessah, I.; Van de Water, J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav. Immun., 2011, 25(1), 40-45.
[http://dx.doi.org/10.1016/j.bbi.2010.08.003] [PMID: 20705131]
[40]
Careaga, M.; Noyon, T.; Basuta, K.; Van de Water, J.; Tassone, F.; Hagerman, R.J.; Ashwood, P. Group I metabotropic glutamate receptor mediated dynamic immune dysfunction in children with fragile X syndrome. J. Neuroinflammation, 2014, 11(1), 110.
[http://dx.doi.org/10.1186/1742-2094-11-110] [PMID: 24942544]
[41]
Lehtimäki, K.A.; Liimatainen, S.; Peltola, J.; Arvio, M. The serum level of interleukin-6 in patients with intellectual disability and refractory epilepsy. Epilepsy Res., 2011, 95(1-2), 184-187.
[http://dx.doi.org/10.1016/j.eplepsyres.2011.03.004] [PMID: 21530175]
[42]
Carmeli, E.; Beiker, R.; Morad, M. Nitric oxide and interlukin-6 levels in intellectual disability adults with epilepsy. Res. Dev. Disabil., 2009, 30(3), 567-571.
[http://dx.doi.org/10.1016/j.ridd.2008.08.004] [PMID: 18834707]
[43]
Malaeb, S.; Dammann, O. Fetal inflammatory response and brain injury in the preterm newborn. J. Child Neurol., 2009, 24(9), 1119-1126.
[http://dx.doi.org/10.1177/0883073809338066] [PMID: 19605775]
[44]
Dammann, O.; O’Shea, T.M. Cytokines and perinatal brain damage. Clin. Perinatol., 2008, 35(4), 643-663.
[http://dx.doi.org/10.1016/j.clp.2008.07.011] [PMID: 19026332]
[45]
Shalak, L.F.; Laptook, A.R.; Jafri, H.S.; Ramilo, O.; Perlman, J.M. Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics, 2002, 110(4), 673-680.
[http://dx.doi.org/10.1542/peds.110.4.673] [PMID: 12359779]
[46]
Yoon, B.H.; Jun, J.K.; Romero, R.; Gomez, R. Amniotic fluid inflammatory cytokines (interleukin-6, interleukin-l[3, and tumor necrosis factor-s), neonatal brain white matter lesions, and cerebral palsy. Am. J. Obstet. Gynecol., 1997, 177(1), 8.
[http://dx.doi.org/10.1016/S0002-9378(97)70432-0] [PMID: 9240575]
[47]
Li, G.; Bauer, S.; Nowak, M.; Norwood, B.; Tackenberg, B.; Rosenow, F.; Knake, S.; Oertel, W.H.; Hamer, H.M. Cytokines and epilepsy. Seizure, 2011, 20(3), 249-256.
[http://dx.doi.org/10.1016/j.seizure.2010.12.005] [PMID: 21216630]
[48]
Ravizza, T.; Vezzani, A. Status epilepticus induces time-dependent neuronal and astrocytic expression of interleukin-1 receptor type I in the rat limbic system. Neuroscience, 2006, 137(1), 301-308.
[http://dx.doi.org/10.1016/j.neuroscience.2005.07.063] [PMID: 16289587]
[49]
Vitkovic, L.; Bockaert, J.; Jacque, C. “Inflammatory” cytokines: neuromodulators in normal brain? J. Neurochem., 2000, 74(2), 457-471.
[http://dx.doi.org/10.1046/j.1471-4159.2000.740457.x] [PMID: 10646496]
[50]
Hohlfeld, R.; Kerschensteiner, M.; Meinl, E. Dual role of inflammation in CNS disease. Neurology, 2007, 68(22), S58-S63.
[http://dx.doi.org/10.1212/01.wnl.0000275234.43506.9b]
[51]
Garlanda, C.; Dinarello, C.A.; Mantovani, A. The interleukin-1 family: back to the future. Immunity, 2013, 39(6), 1003-1018.
[http://dx.doi.org/10.1016/j.immuni.2013.11.010] [PMID: 24332029]
[52]
Gutierrez, E.G.; Banks, W.A.; Kastin, A.J. Murine tumor necrosis factor alpha is transported from blood to brain in the mouse. J. Neuroimmunol., 1993, 47(2), 169-176.
[http://dx.doi.org/10.1016/0165-5728(93)90027-V] [PMID: 8370768]
[53]
Yang, G-Y.; Gong, C.; Qin, Z.; Liu, X-H.; Lorris Betz, A. Tumor necrosis factor alpha expression produces increased blood-brain barrier permeability following temporary focal cerebral ischemia in mice. Brain Res. Mol. Brain Res., 1999, 69(1), 135-143.
[http://dx.doi.org/10.1016/S0169-328X(99)00007-8] [PMID: 10350645]
[54]
Monica, Ek.; David, E.; Sipra, S.; Anders, B.; Per-Johan, J.; Anders, E-D. Pathway across the blood-brain barrier. Nature, 2001, 410, 430-431.
[http://dx.doi.org/10.1038/35068632]
[55]
Quan, N.; Banks, W.A. Brain-immune communication pathways. Brain Behav. Immun., 2007, 21(6), 727-735.
[http://dx.doi.org/10.1016/j.bbi.2007.05.005] [PMID: 17604598]
[56]
Saha, R.N.; Liu, X.; Pahan, K. Up-regulation of BDNF in astrocytes by TNF-α: a case for the neuroprotective role of cytokine. J. Neuroimmune Pharmacol., 2006, 1(3), 212-222.
[http://dx.doi.org/10.1007/s11481-006-9020-8] [PMID: 18040799]
[57]
Bains, J.S.; Oliet, S.H.R. Glia: they make your memories stick! Trends Neurosci., 2007, 30(8), 417-424.
[http://dx.doi.org/10.1016/j.tins.2007.06.007] [PMID: 17631972]
[58]
Trotta, M.B.; Serro Azul, J.B.; Wajngarten, M.; Fonseca, S.G.; Goldberg, A.C.; Kalil, J.E. Inflammatory and immunological parameters in adults with Down syndrome. Immun. Ageing, 2011, 8(1), 4.
[http://dx.doi.org/10.1186/1742-4933-8-4] [PMID: 21496308]
[59]
Baron, R.; Nemirovsky, A.; Harpaz, I.; Cohen, H.; Owens, T.; Monsonego, A. IFN-γ enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer’s disease. FASEB J., 2008, 22(8), 2843-2852.
[http://dx.doi.org/10.1096/fj.08-105866] [PMID: 18390924]
[60]
Yaguchi, M.; Ohta, S.; Toyama, Y.; Kawakami, Y.; Toda, M. Functional recovery after spinal cord injury in mice through activation of microglia and dendritic cells after IL-12 administration. J. Neurosci. Res., 2008, 86(9), 1972-1980.
[http://dx.doi.org/10.1002/jnr.21658] [PMID: 18438913]
[61]
Carmeli, E.; Imam, B.; Bachar, A.; Merrick, J. Inflammation and oxidative stress as biomarkers of premature aging in persons with intellectual disability. Res. Dev. Disabil., 2012, 33(2), 369-375.
[http://dx.doi.org/10.1016/j.ridd.2011.10.002] [PMID: 22119683]
[62]
Van Dijck, A.; Barbosa, S.; Bermudez-Martin, P.; Khalfallah, O.; Gilet, C.; Martinuzzi New, E.; Elinck, E.; Kooy, F.; Glaichenhaus, N.; Davidovic, L. Reduced serum levels of pro-inflammatory chemokines in fragile X syndrome., BMC Neurol., 2020, 20(1), 138..
[http://dx.doi.org/10.1186/s12883-020-01715-2 ] [PMID: 32295518]
[63]
Stuart, M.J.; Singhal, G.; Baune, B.T. Systematic review of the neurobiological relevance of chemokines to psychiatric disorders. Front. Cell. Neurosci., 2015, 9, 357.
[http://dx.doi.org/10.3389/fncel.2015.00357] [PMID: 26441528]
[64]
Cross, A.K.; Woodroofe, M.N. Chemokines induce migration and changes in actin polymerization in adult rat brain microglia and a human fetal microglial cell line in vitro. J. Neurosci. Res., 1999, 55(1), 17-23.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19990101)55:1<17:AID-JNR3>3.0.CO;2-J]]
[65]
Selenica, M.L.; Alvarez, J.A.; Nash, K.R.; Lee, D.C.; Cao, C.; Lin, X.; Reid, P.; Mouton, P.R.; Morgan, D.; Gordon, M.N. Diverse activation of microglia by chemokine (C-C motif) ligand 2 overexpression in brain. J. Neuroinflammation, 2013, 10(1), 86.
[http://dx.doi.org/10.1186/1742-2094-10-86] [PMID: 23866683]
[66]
Skuljec, J.; Sun, H.; Pul, R.; Bénardais, K.; Ragancokova, D.; Moharregh-Khiabani, D.; Kotsiari, A.; Trebst, C.; Stangel, M. CCL5 induces a pro-inflammatory profile in microglia in vitro. Cell. Immunol., 2011, 270(2), 164-171.
[http://dx.doi.org/10.1016/j.cellimm.2011.05.001] [PMID: 21620385]
[67]
Widera, D.; Holtkamp, W.; Entschladen, F.; Niggemann, B.; Zänker, K.; Kaltschmidt, B.; Kaltschmidt, C. MCP-1 induces migration of adult neural stem cells. Eur. J. Cell Biol., 2004, 83(8), 381-387.
[http://dx.doi.org/10.1078/0171-9335-00403] [PMID: 15506562]

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