Monoamine oxidase-B activity is not involved in the neuroinflammatory response elicited by a focal freeze brain injury.

Abstract

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.

• Authors: Elisenda Sanz, Albert Quintana, Tony Valente, Yasmina Manso, Juan Hidalgo, Mercedes Unzeta
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 87 Issue 3 Pg. 784-94 (Feb 15 2009) ISSN: 1097-4547 [Electronic] United States
• PMID: 18831059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Cell Adhesion Molecules
• Fas protein, mouse
• Glial Fibrillary Acidic Protein
• Indoles
• Macrophage-1 Antigen
• Monoamine Oxidase Inhibitors
• N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine
• Nerve Tissue Proteins
• fas Receptor
• glial fibrillary astrocytic protein, mouse
• Monoamine Oxidase
• Receptor-Interacting Protein Serine-Threonine Kinases
• Caspase 1

Topics

• Animals
• Brain Injuries (drug therapy, enzymology, genetics, immunology)
• Caspase 1 (metabolism)
• Cell Adhesion Molecules (metabolism)
• Cell Death (physiology)
• Encephalitis (drug therapy, enzymology)
• Freezing
• Genes, p53 (drug effects)
• Glial Fibrillary Acidic Protein
• Indoles (pharmacology)
• Macrophage-1 Antigen (metabolism)
• Mice
• Mice, Inbred Strains
• Monoamine Oxidase (metabolism)
• Monoamine Oxidase Inhibitors (pharmacology)
• Motor Activity (drug effects)
• Nerve Tissue Proteins (metabolism)
• Receptor-Interacting Protein Serine-Threonine Kinases (metabolism)
• fas Receptor (metabolism)