Monoamine oxidase-B activity is not involved in the neuroinflammatory response elicited by a focal freeze brain injury.
Cryolesion of the frontoparietal cortex in mice is a well-described brain injury paradigm that results in increased astrogliosis surrounding the lesion site and is accompanied by a prominent increase in the MAO-B levels in astrocytes. Whether these increased MAO-B levels contribute to cellular damage or modulate reactive astrocytosis remains unclear. MAO-B activity may contribute to cellular damage, since its metabolism products are highly toxic to the cells. Additionally, it has been suggested that MAO-B inhibition may regulate astrocytic reaction. In this study, we have determined the relative contribution of MAO-B activity to the outcome following freeze injury. Freeze injury induced a prominent increase of several inflammatory markers, including ICAM, Mac-1, EB22, and GFAP. Inhibition of MAO-B activity using the selective inhibitor PF9601N did not reduce this cryolesion-induced inflammatory response. Additional data revealed that the expression of several cryolesion-induced cell death genes, such as Fas, Rip, p53, and ICE, was not reduced in PF9601N-treated mice, evidencing that MAO-B activity did not contribute to cryolesion-induced cell death. Definitive functional analysis of the mice using the ladder beam task revealed that MAO-B inhibition did not improve the cryolesion-induced motor impairment. These data strongly suggest that, although MAO-B is highly expressed in the area surrounding the lesion site, its activity does not contribute to the cellular damage or play any role in regulating astrocytic reactivity.
Sanz
Elisenda
E
Institut de Neurociències i Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. elisenda.sanz@uab.es
Quintana
Albert
A
Valente
Tony
T
Manso
Yasmina
Y
Hidalgo
Juan
J
Unzeta
Mercedes
M
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D020170:Caspase 1 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D004660:Encephalitis / Q000188:drug therapy / Q000201:enzymology; D005615:Freezing; D016158:Genes, p53 / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D015815:Cell Adhesion Molecules; C491899:Fas protein, mouse; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D016177:Macrophage-1 Antigen; D008996:Monoamine Oxidase Inhibitors; C470996:N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine; D009419:Nerve Tissue Proteins; D019014:fas Receptor; C528900:glial fibrillary astrocytic protein, mouse; D008995:Monoamine Oxidase; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D020170:Caspase 1