Monocyte chemoattractant protein-1 upregulates gaba-induced current: Evidence of modified GABAA subunit composition in cortical neurons from the G93A mouse model of Amyotrophic Lateral Sclerosis

Neuropharmacology

Volumn 73, Issue , 2013, Pages 247-260

  Caioli, Silvia ^b   Pieri, Massimo ^a   Antonini, Alessia ^a   Guglielmotti, Angelo ^c   Severini, Cinzia ^d   Zona, Cristina ^a,b  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^c Università Politecnica delle Marche ACRAF Gruppo Angelini   (Italy)

^d CNR   (Italy)

Author keywords

ALS; Electrophysiology; GABA receptor modulator; GABA induced current; Immunosystem; Neurodegeneration

Indexed keywords

4 AMINOBUTYRIC ACID; 4 AMINOBUTYRIC ACID A RECEPTOR; BENZODIAZEPINE RECEPTOR; FLUMAZENIL; MONOCYTE CHEMOTACTIC PROTEIN 1;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN CELL; BRAIN CORTEX; CONTROLLED STUDY; ELECTROPHYSIOLOGY; EVOKED RESPONSE; EXCITATORY POSTSYNAPTIC POTENTIAL; EXCITOTOXICITY; FEMALE; HUMAN; MALE; MOUSE; NERVE DEGENERATION; NEUROMODULATION; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS INHIBITION; SPINAL CORD NERVE CELL; UPREGULATION;

ALS; ELECTROPHYSIOLOGY; GABA RECEPTOR MODULATOR; GABA-INDUCED CURRENT; IMMUNOSYSTEM; NEURODEGENERATION;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; CELLS, CULTURED; CEREBRAL CORTEX; CHEMOKINE CCL2; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FLUMAZENIL; GABA-A RECEPTOR ANTAGONISTS; GAMMA-AMINOBUTYRIC ACID; HUMANS; MALE; MEMBRANE POTENTIALS; MICE; MICE, TRANSGENIC; NEURONS; PROTEIN SUBUNITS; RECEPTORS, GABA-A; SPINAL CORD;

EID: 84885169396     PISSN: 00283908     EISSN: 18737064     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2013.05.045     Document Type: Article

References (121)

1. Abdullah, J.M., Zhang, J., 2013. The GABA a receptor subunits heterologously expressed in xenopus oocytes. Mini Rev. Med. Chem. 13, 744-748.
2. Alexianu, M.E., Kozovska, M., Appel, S.H., 2001. Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology 57, 1282-1289.
3. Almer, G., Guegan, C, Teismann, P., Naini, A., Rosoklija, G., Hays, A.P., Chen, C, Przedborski, S., 2001. Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann. Neurol. 49, 176-185.
4. Appel, S.H., Zhao, W., Beers, D.R., Henkel, J.S., 2011. The microglial-motoneuron dialogue in ALS. Acta Myol. 30, 4-8.
5. Atack, J.R., 2011. GABAA receptor subtype-selective modulators. I. alpha2/alpha3-selective agonists as non-sedating anxiolytics. Curr. Top Med. Chem. 11, 1176-1202.
6. Azizi, G., Mirshafiey, A., 2012. The potential role of proinflammatory and antiinflammatory cytokines in Alzheimer disease pathogenesis. Immunopharmacol Immunotoxicol 34, 881-895.
7. 2+ network. J. Cell Biol. 136, 833-844.
8. Babot, Z., Cristofol, R., Sunol, C, 2005. Excitotoxic death induced by released glutamate in depolarized primary cultures of mouse cerebellar granule cells is dependent on GABAA receptors and niflumic acid-sensitive chloride channels. Eur. J. Neurosci. 21, 103-112.
9. Barnard, E.A., Skolnick, P., Olsen, R.W., Mohler, H., Sieghart, W., Biggio, G., Braestrup, C, Bateson, A.N., Langer, S.Z., 1998. International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function. Pharmacol. Rev. 50, 291-313.
10. Baron, P., Bussini, S., Cardin, V., Corbo, M., Conti, G., Galimberti, D., Scarpini, E., Bresolin, N., Wharton, S.B., Shaw, P.J., Silani, V., 2005. Production of monocyte chemoattractant protein-1 in amyotrophic lateral sclerosis. Muscle Nerve 32, 541-544.
11. Beauchamp, C, Fridovich, I., 1971. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 44, 276-287.
12. Beers, D.R., Henkel, J.S., Xiao, Q., Zhao, W., Wang, J., Yen, A.A., Siklos, L., McKercher, S.R., Appel, S.H., 2006. Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA 103, 16021-16026.
13. Belkouch, M., Dansereau, M.A., Reaux-Le Goazigo, A., Van Steenwinckel, J., Beaudet, N., Chraibi, A., Melik-Parsadaniantz, S., Sarret, P., 2011. The chemokine CCL2 increases Nav1.8 sodium channel activity in primary sensory neurons through a Gbetagamma-dependent mechanism. J. Neurosci. 31, 18381-18390.
14. Ben-Ari, Y., Gaiarsa, J.L, Tyzio, R., Khazipov, R., 2007. GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol. Rev. 87, 1215-1284.
15. Bento-Abreu, A., Van Damme, P., Van Den Bosch, L., Robberecht, W, 2010. The neurobiology of amyotrophic lateral sclerosis. Eur. J. Neurosci. 31, 2247-2265.
16. Bilsland, L.G., Sahai, E., Kelly, G., Golding, M., Greensmith, L., Schiavo, G., 2010. Deficits in axonal transport precede ALS symptoms in vivo. Proc. Natl. Acad. Sci. USA 107, 20523-20528.
17. Boillee, S., Yamanaka, K., Lobsiger, CS., Copeland, N.G., Jenkins, N.A., Kassiotis, G., Kollias, G., Cleveland, D.W., 2006. Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312, 1389-1392.
18. Bruijn, LI., Miller, T.M., Cleveland, D.W., 2004. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu. Rev. Neurosci. 27, 723-749.
19. Caioli, S., Pieri, M., Antonini, A., Guglielmotti, A., Zona, C, 2011. Monocyte chemoattractant protein-1 up modulates gaba-induced currents in cortical neurons from a murine model of amyotrophic lateral sclerosis. In: 8th IBRO world Congress in Neuroscience, Florence.
20. 2+ concentration in transfected neuroblastoma SH-SY5Y cells. FEBS Lett. 414, 365-368.
21. Carriedo, S.G., Yin, H.Z., Weiss, J.H., 1996. Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury in vitro. J. Neurosci. 16, 4069-4079.
22. Carunchio, I., Curcio, L, Pieri, M., Pica, F., Caioli, S., Viscomi, M.T., Molinari, M., Canu, N., Bernardi, G., Zona, C, 2010. Increased levels of p70S6 phosphorylation in the G93A mouse model of Amyotrophic Lateral Sclerosis and in valine-exposed cortical neurons in culture. Exp. Neurol. 226, 218-230.
23. Carunchio, I., Mollinari, C, Pieri, M., Merlo, D., Zona, C, 2008. GAB(A) receptors present higher affinity and modified subunit composition in spinal motor neurons from a genetic model of amyotrophic lateral sclerosis. Eur. J. Neurosci. 28, 1275-1285.
24. Cash, D.J., Serfozo, P., Allan, A.M., 1997. Desensitization of a gamma-aminobutyric acid type A receptor in rat is increased by chronic treatment with chlordiazepoxide: a molecular mechanism of dependence. J. Pharmacol. Exp. Ther. 283, 704-711.
25. Chang, Q., Martin, L.J., 2011. Glycine receptor channels in spinal motoneurons are abnormal in a transgenic mouse model of amyotrophic lateral sclerosis. J. Neurosci. 31, 2815-2827.
26. 2+-independent excitotoxic neurodegeneration in isolated retina, an intact neural net: a role for Cl and inhibitory transmitters. Mol. Pharmacol. 53, 564-572.
27. Cleveland, D.W., Rothstein, J.D., 2001. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci. 2, 806-819.
28. Collins, L.M., Toulouse, A., Connor, T.J., Nolan, Y.M., 2012. Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease. Neuropharmacology 62, 2154-2168.
29. D'Hulst, C, Atack, J.R., Kooy, R.F., 2009. The complexity of the GABAA receptor shapes unique pharmacological profiles. Drug Discov. Today 14, 866-875.
30. 2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J. Neurochem. 96, 1349-1361.
31. De Vos, K.J., Chapman, A.L, Tennant, M.E., Manser, C, Tudor, E.L., Lau, K.F., Brownlees, J., Ackerley, S., Shaw, P.J., McLoughlin, D.M., Shaw, CE., Leigh, P.N., Miller, CC, Grierson, A.J., 2007. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum. Mol. Genet. 16, 2720-2728.
32. Deshmane, S.L., Kremlev, S., Amini, S., Sawaya, B.E., 2009. Monocyte chemoattractant protein-1 (MCP-1): an overview. J. Interferon Cytokine Res. 29, 313-326.
33. Engelhardt, J.I., Appel, S.H., 1990. IgG reactivity in the spinal cord and motor cortex in amyotrophic lateral sclerosis. Arch. Neurol. 47, 1210-1216.
34. Engelhardt, J.I., Tajti, J., Appel, S.H., 1993. Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch. Neurol. 50, 30-36.
35. Fisher, J.L., Hinkle, D.J., Macdonald, R.L, 2000. Loreclezole inhibition of recombinant alpha1beta1gamma2L GABA(A) receptor single channel currents. Neuropharmacology 39, 235-245.
36. Foerster, B.R., Callaghan, B.C., Petrou, M., Edden, R.A., Chenevert, TL, Feldman, E.L., 2012. Decreased motor cortex gamma-aminobutyric acid in amyotrophic lateral sclerosis. Neurology 78, 1596-1600.
37. Foran, E., Trotti, D., 2009. Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid. Redox Signal 11, 1587-1602.
38. Frere, R.C., Macdonald, R.L., Young, A.B., 1982. GABA binding and bicuculline in spinal cord and cortical membranes from adult rat and from mouse neurons in cell culture. Brain Res. 244, 145-153.
39. Fritschy, J.M., Brunig, I., 2003. Formation and plasticity of GABAergic synapses: physiological mechanisms and pathophysiological implications. Pharmacol. Ther. 98, 299-323.
40. Fuchs, A., Ringer, C, Bilkei-Gorzo, A., Weihe, E., Roeper, J., Schutz, B., 2010. Down-regulation of the potassium chloride cotransporter KCC2 in vulnerable motoneurons in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 69, 1057-1070.
41. Fung, A., Vizcaychipi, M., Lloyd, D., Wan, Y, Ma, D., 2012. Central nervous system inflammation in disease related conditions: mechanistic prospects. Brain Res. 1446, 144-155.
42. Gao, H., Smith, B.N., 2010. Zolpidem modulation of phasic and tonic GABA currents in the rat dorsal motor nucleus of the vagus. Neuropharmacology 58, 1220-1227.
43. Gosselin, R.D., Varela, C, Banisadr, G., Mechighel, P., Rostene, W, Kitabgi, P., Melik-Parsadaniantz, S., 2005. Constitutive expression of CCR2 chemokine receptor and inhibition by MCP-1/CCL2 of GABA-induced currents in spinal cord neurones. J. Neurochem. 95, 1023-1034.
44. Grewal, R.P., Morgan, T.E., Finch, CE., 1999. C1qB and clusterin mRNA increase in association with neurodegeneration in sporadic amyotrophic lateral sclerosis. Neurosci. Lett. 271, 65-67.
45. 2+ transients in cultured spinal motor neurons. Cell Calcium 42, 59-69.
46. Gruzman, A., Wood, WL, Alpert, E., Prasad, M.D., Miller, R.G., Rothstein, J.D., Bowser, R., Hamilton, R., Wood, T.D., Cleveland, D.W., Lingappa, V.R., Liu, J., 2007. Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA 104, 12524-12529.
47. Guatteo, E., Carunchio, I., Pieri, M., Albo, F., Canu, N., Mercuri, N.B., Zona, C, 2007. Altered calcium homeostasis in motor neurons following AMPA receptor but not voltage-dependent calcium channels' activation in a genetic model of amyotrophic lateral sclerosis. Neurobiol. Dis. 28, 90-100.
48. Gurney, M.E., Pu, H., Chiu, A.Y, Dal Canto, M. C, Polchow, CY, Alexander, D.D., Caliendo, J., Hentati, A., Kwon, YW, Deng, H.X., et al., 1994. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264, 1772-1775.
49. Hall, B.J., Chebib, M., Hanrahan, J.R., Johnston, G.A., 2004. Flumazenil-independent positive modulation of gamma-aminobutyric acid action by 6-methylflavone at human recombinant alpha1beta2gamma2L and alpha1beta2 GABAA receptors. Eur. J. Pharmacol. 491, 1-8.
50. Hansen, S.L., Ebert, B., Fjalland, B., Kristiansen, U., 2001. Effects of GABA(A) receptor partial agonists in primary cultures of cerebellar granule neurons and cerebral cortical neurons reflect different receptor subunit compositions. Br. J. Pharmacol. 133, 539-549.
51. Hatton, C.J., Shelley, C., Brydson, M., Beeson, D., Colquhoun, D., 2003. Properties of the human muscle nicotinic receptor, and of the slow-channel myasthenic syndrome mutant epsilon L221F, inferred from maximum likelihood fits. J. Physiol. 547, 729-760.
52. Henkel, J.S., Beers, D.R., Siklos, L., Appel, S.H., 2006. The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS. Mol. Cell Neurosci. 31, 427-437.
53. Henkel, J.S., Engelhardt, J.I., Siklos, L., Simpson, E.P., Kim, S.H., Pan, T., Goodman, J.C., Siddique, T., Beers, D.R., Appel, S.H., 2004. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann. Neurol. 55, 221-235.
54. Hollis, D.M., Boyd, S.K., 2003. Characterization of the GABA(A) receptor in the brain of the adult male bullfrog, Rana catesbeiana. Brain Res. 992, 69-75.
55. Ince, P.G., Shaw, P.J., Slade, J.Y., Jones, C., Hudgson, P., 1996. Familial amyotrophic lateral sclerosis with a mutation in exon 4 of the Cu/Zn superoxide dismutase gene: pathological and immunocytochemical changes. Acta Neuropathol. 92, 395-403.
56. Inoue, H., Okada, Y., 2007. Roles of volume-sensitive chloride channel in excitotoxic neuronal injury. J. Neurosci. 27, 1445-1455.
57. Johnston, J.A., Dalton, M.J., Gurney, M.E., Kopito, R.R., 2000. Formation of high molecular weight complexes of mutant Cu, Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U S A 97, 12571-12576.
58. Kao, D.J., Li, A.H., Chen, J.C., Luo, R.S., Chen, Y.L., Lu, J.C., Wang, H.L., 2012. CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Nav1.8 sodium channels in dorsal root ganglion neurons. J. Neuroinflammation 9, 189.
59. Kawamata, T., Akiyama, H., Yamada, T., McGeer, P.L., 1992. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am. J. Pathol. 140, 691-707.
60. Keep, M., Elmer, E., Fong, K.S., Csiszar, K., 2001. Intrathecal cyclosporin prolongs survival of late-stage ALS mice. Brain Res. 894, 327-331.
61. Kiernan, M.C., Vucic, S., Cheah, B.C., Turner, M.R., Eisen, A., Hardiman, O., Burrell, J.R., Zoing, M.C., 2011. Amyotrophic lateral sclerosis. Lancet 377, 942-955.
62. Korpi, E.R., Grunder, G., Luddens, H., 2002. Drug interactions at GABA(A) receptors. Prog. Neurobiol. 67, 113-159.
63. Krogsgaard-Larsen, P., Krogsgaard-Larsen, P., Arnt, J., Arnt, J., 1979. GABA receptor agonists: relationship between structure and biological activity in vivo and in vitro. Adv. Exp. Med. Biol. 123, 303-321.
64. Kuhle, J., Lindberg, R.L., Regeniter, A., Mehling, M., Steck, A.J., Kappos, L., Czaplinski, A., 2009. Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur. J. Neurol. 16, 771-774.
65. Kuo, J.J., Siddique, T., Fu, R., Heckman, C.J., 2005. Increased persistent Na(+) current and its effect on excitability in motoneurones cultured from mutant SOD1 mice. J. Physiol. 563, 843-854.
66. Kwiatkowski Jr., T.J., Bosco, D.A., Leclerc, A.L., Tamrazian, E., Vanderburg, C.R., Russ, C., Davis, A., Gilchrist, J., Kasarskis, E.J., Munsat, T., Valdmanis, P., Rouleau, G.A., Hosler, B.A., Cortelli, P., de Jong, P.J., Yoshinaga, Y., Haines, J.L., Pericak-Vance, M.A., Yan, J., Ticozzi, N., Siddique, T., McKenna-Yasek, D., Sapp, P.C., Horvitz, H.R., Landers, J.E., Brown Jr., R.H., 2009. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205-1208.
67. Lampson, L.A., Kushner, P.D., Sobel, R.A., 1990. Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. Ann. Neurol. 28, 365-372.
68. Lloyd, C.M., Richardson, M.P., Brooks, D.J., Al-Chalabi, A., Leigh, P.N., 2000. Extramotor involvement in ALS: PET studies with the GABA(A) ligand [(11)C]flumazenil. Brain 123 (Pt 11), 2289-2296.
69. Marinkovic, P., Reuter, M.S., Brill, M.S., Godinho, L., Kerschensteiner, M., Misgeld, T., 2012. Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U S A 109, 4296-4301.
70. Martorana, F., Brambilla, L., Valori, C.F., Bergamaschi, C., Roncoroni, C., Aronica, E., Volterra, A., Bezzi, P., Rossi, D., 2012. The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intra-cellular calcium signals. Hum. Mol. Genet. 21, 826-840.
71. McGeer, P.L., Itagaki, S., McGeer, E.G., 1988. Expression of the histocompatibility glycoprotein HLA-DR in neurological disease. Acta Neuropathol. 76, 550-557.
72. Melgarejo, E., Medina, M.A., Sanchez-Jimenez, F., Urdiales, J.L., 2009. Monocyte chemoattractant protein-1: a key mediator in inflammatory processes. Int. J. Biochem. Cell Biol. 41, 998-1001.
73. Mitchell, R.M., Simmons, Z., Beard, J.L., Stephens, H.E., Connor, J.R., 2010. Plasma biomarkers associated with ALS and their relationship to iron homeostasis. Muscle Nerve 42, 95-103.
74. Momosaki, S., Hosoi, R., Abe, K., Inoue, O., 2010. Remarkable selectivity of the in vivo binding of [3H]Ro15-4513 to alpha5 subtype of benzodiazepine receptor in the living mouse brain. Synapse 64, 928-936.
75. Nagata, T., Nagano, I., Shiote, M., Narai, H., Murakami, T., Hayashi, T., Shoji, M., Abe, K., 2007. Elevation of MCP-1 and MCP-1/VEGF ratio in cerebrospinal fluid of amyotrophic lateral sclerosis patients. Neurol. Res. 29, 772-776.
76. Nani, F., Cifra, A., Nistri, A., 2010. Transient oxidative stress evokes early changes in the functional properties of neonatal rat hypoglossal motoneurons in vitro. Eur. J. Neurosci. 31, 951-966.
77. Nieto-Gonzalez, J.L., Moser, J., Lauritzen, M., Schmitt-John, T., Jensen, K., 2010. Reduced GABAergic inhibition explains cortical hyperexcitability in the wobbler mouse model of ALS. Cereb. Cortex 21, 625-635.
78. Oh, D.J., Dichter, M.A., 1992. Desensitization of GABA-induced currents in cultured rat hippocampal neurons. Neuroscience 49, 571-576.
79. Olsen, R.W., Sieghart, W., 2009. GABA A receptors: subtypes provide diversity of function and pharmacology. Neuropharmacology 56, 141-148.
80. Pasinelli, P., Brown, R.H., 2006. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev. Neurosci. 7, 710-723.
81. Petri, S., Kollewe, K., Grothe, C., Hori, A., Dengler, R., Bufler, J., Krampfl, K., 2006. GABA(A)-receptor mRNA expression in the prefrontal and temporal cortex of ALS patients. J. Neurol. Sci. 250, 124-132.
82. Petri, S., Krampfl, K., Hashemi, F., Grothe, C., Hori, A., Dengler, R., Bufler, J., 2003. Distribution of GABAA receptor mRNA in the motor cortex of ALS patients. J. Neuropathol. Exp. Neurol. 62, 1041-1051.
83. Phani, S., Loike, J.D., Przedborski, S., 2012. Neurodegeneration and inflammation in Parkinson's disease. Parkinsonism Relat. Disord. 18 (Suppl. 1), S207-S209.
84. Philips, T., Robberecht, W., 2011. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 10, 253-263.
85. Pieri, M., Carunchio, I., Curcio, L., Mercuri, N.B., Zona, C., 2009. Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosis. Exp. Neurol. 215, 368-379.
86. Pirker, S., Schwarzer, C., Wieselthaler, A., Sieghart, W., Sperk, G., 2000. GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101, 815-850.
87. Romme Christensen, J., Bornsen, L., Khademi, M., Olsson, T., Jensen, P.E., Sorensen, P.S., Sellebjerg, F., 2012. CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis. Mult. Scler. 19, 877-884.
88. Rothman, S.M., 1985. The neurotoxicity of excitatory amino acids is produced by passive chloride influx. J. Neurosci. 5, 1483-1489.
89. Rowland, L.P., Shneider, N.A., 2001. Amyotrophic lateral sclerosis. N. Engl. J. Med. 344, 1688-1700.
90. Rudolph, U., Knoflach, F., 2011. Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes. Nat. Rev. Drug Discov. 10, 685-697.
91. Sargsyan, S.A., Blackburn, D.J., Barber, S.C., Monk, P.N., Shaw, P.J., 2009. Mutant SOD1 G93A microglia have an inflammatory phenotype and elevated production of MCP-1. Neuroreport 20, 1450-1455.
92. Schiffer, D., Cordera, S., Cavalla, P., Migheli, A., 1996. Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis. J. Neurol. Sci. (Suppl. 139), 27-33.
93. Sekizawa, T., Openshaw, H., Ohbo, K., Sugamura, K., Itoyama, Y., Niland, J.C., 1998. Cerebrospinal fluid interleukin 6 in amyotrophic lateral sclerosis: immunological parameter and comparison with inflammatory and non-inflammatory central nervous system diseases. J. Neurol. Sci. 154, 194-199.
94. Sharkey, L.M., Czajkowski, C., 2008. Individually monitoring ligand-induced changes in the structure of the GABAA receptor at benzodiazepine binding site and non-binding-site interfaces. Mol. Pharmacol. 74, 203-212.
95. Sieghart, W., Sperk, G., 2002. Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr. Top Med. Chem. 2, 795-816.
96. Skaper, S.D., Giusti, P., Facci, L., 2012. Microglia and mast cells: two tracks on the road to neuroinflammation. Faseb J. 26, 3103-3117.
97. Sun, J.H., Yang, B., Donnelly, D.F., Ma, C., LaMotte, R.H., 2006. MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia. J. Neurophysiol. 96, 2189-2199.
98. Sunico, C.R., Dominguez, G., Garcia-Verdugo, J.M., Osta, R., Montero, F., Moreno-Lopez, B., 2010. Reduction in the motoneuron inhibitory/excitatory synaptic ratio in an early-symptomatic mouse model of amyotrophic lateral sclerosis. Brain Pathol. 21, 1-15.
99. Tamura, N., Kuwabara, S., Misawa, S., Kanai, K., Nakata, M., Sawai, S., Hattori, T., 2006. Increased nodal persistent Na+ currents in human neuropathy and motor neuron disease estimated by latent addition. Clin. Neurophysiol. 117, 2451-2458.
100. Tradewell, M.L., Cooper, L.A., Minotti, S., Durham, H.D., 2011. Calcium dysregulation, mitochondrial pathology and protein aggregation in a culture model of amyotrophic lateral sclerosis: mechanistic relationship and differential sensitivity to intervention. Neurobiol. Dis. 42, 265-275.
101. Trincavelli, M.L., Da Pozzo, E., Daniele, S., Martini, C., 2012. The GABAA-BZR complex as target for the development of anxiolytic drugs. Curr. Top Med. Chem. 12, 254-269.
102. Troost, D., Van den Oord, J.J., Vianney de Jong, J.M., 1990. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol. Appl. Neurobiol. 16, 401-410.
103. Turner, M.R., Cagnin, A., Turkheimer, F.E., Miller, C.C., Shaw, C.E., Brooks, D.J., Leigh, P.N., Banati, R.B., 2004. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol. Dis. 15, 601-609.
104. 2+-dependent AMPA receptor-mediated motoneuron death. J. Neurosci. 23, 4942-4950.
105. Van Den Bosch, L., Van Damme, P., Bogaert, E., Robberecht, W., 2006. The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim. Biophys. Acta 1762, 1068-1082.
106. van Zundert, B., Peuscher, M.H., Hynynen, M., Chen, A., Neve, R.L., Brown Jr, R.H., Constantine-Paton, M., Bellingham, M.C., 2008. Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J. Neurosci. 28, 10864-10874.
107. Vance, C., Rogelj, B., Hortobagyi, T., De Vos, K.J., Nishimura, A.L., Sreedharan, J., Hu, X., Smith, B., Ruddy, D., Wright, P., Ganesalingam, J., Williams, K.L., Tripathi, V., Al-Saraj, S., Al-Chalabi, A., Leigh, P.N., Blair, I.P., Nicholson, G., de Belleroche, J., Gallo, J.M., Miller, C.C., Shaw, C.E., 2009. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208-1211.
108. Vucic, S., Cheah, B.C., Yiannikas, C., Kiernan, M.C., 2011. Cortical excitability distinguishes ALS from mimic disorders. Clin. Neurophysiol. 122, 1860-1866.
109. Vucic, S., Ziemann, U., Eisen, A., Hallett, M., Kiernan, M.C., 2012. Transcranial magnetic stimulation and amyotrophic lateral sclerosis: pathophysiological insights. J. Neurol. Neurosurg. Psychiatr. [Epub ahead of print].
110. Watanabe, S., Kimura, T., Suenaga, K., Wada, S., Tsuda, K., Kasama, S., Takaoka, T., Kajiyama, K., Takeda, M., Yoshikawa, H., 2009. Decreased chloride levels of cerebrospinal fluid in patients with amyotrophic lateral sclerosis. J. Neurol. Sci. 285, 146-148.
111. Weiss, M., Tikhonov, D., Buldakova, S., 2002. Effect of flumazenil on GABAA receptors in isolated rat hippocampal neurons. Neurochem. Res. 27, 1605-1612.
112. Wieland, H.A., Luddens, H., Seeburg, P.H., 1992. Molecular determinants in GABAA/BZ receptor subtypes. Adv. Biochem. Psychopharmacol. 47, 29-40.
113. Wilms, H., Sievers, J., Dengler, R., Bufler, J., Deuschl, G., Lucius, R., 2003. Intrathecal synthesis of monocyte chemoattractant protein-1 (MCP-1) in amyotrophic lateral sclerosis: further evidence for microglial activation in neurodegeneration. J. Neuroimmunol. 144, 139-142.
114. Wroe, R., Wai-Ling Butler, A., Andersen, P.M., Powell, J.F., Al-Chalabi, A., 2008. ALSOD: the amyotrophic lateral sclerosis online database. Amyotroph. Lateral Scler. 9, 249-250.
115. Yadav, A., Saini, V., Arora, S., 2010. MCP-1: chemoattractant with a role beyond immunity: a review. Clin. Chim. Acta 411, 1570-1579.
116. Yamanaka, K., Boillee, S., Roberts, E.A., Garcia, M.L., McAlonis-Downes, M., Mikse, O.R., Cleveland, D.W., Goldstein, L.S., 2008. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc. Natl. Acad. Sci. U S A 105, 7594-7599.
117. You, H., Altier, C., Zamponi, G.W., 2010a. CCR2 receptor ligands inhibit Cav3.2 T-type calcium channels. Mol. Pharmacol. 77, 211-217.
118. You, H., Kozuska, J.L., Paulsen, I.M., Dunn, S.M., 2010b. Benzodiazepine modulation of the rat GABAA receptor alpha4beta3gamma2L subtype expressed in Xenopus oocytes. Neuropharmacology 59, 527-533.
119. Zhang, R., Gascon, R., Miller, R.G., Gelinas, D.F., Mass, J., Hadlock, K., Jin, X., Reis, J., Narvaez, A., McGrath, M.S., 2005. Evidence for systemic immune system alterations in sporadic amyotrophic lateral sclerosis (sALS). J. Neuroimmunol. 159, 215-224.
120. Zona, C., Caioli, S., Pieri, M., Antonin, A., 2011. GABA-induced Currents are Up-modulated by Monocyte Chemoattractant Protein-1 in Cortical Neurons from the G93A Model of Amyotrophic Lateral Sclerosis. Amyotrophic Lateral Sclerosis - 22nd International Symposium on ALS/MND, Sydney, Australia.
121. Zona, C., Pieri, M., Carunchio, I., 2006. Voltage-dependent sodium channels in spinal cord motor neurons display rapid recovery from fast inactivation in a mouse model of amyotrophic lateral sclerosis. J. Neurophysiol. 96, 3314-3322.