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.

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“…It appears most of the toxicity Monoamine oxidase- β (MAO- β), a mitochondrial enzyme which metabolizes/inhibits dopamine neurotransmitters has been reported to enhance the production of ROS culminating in cell senescence (Maggiorani et al, 2017). Though there exist some opposing views (Damier et al, 1996; Sanz et al, 2009), our study tends to conform with the former. In this study, it was observed that MAO-B was expressed majorly in the synaptic cleft.…”

Characterization of the Molecular Mechanisms Underlying the Chronic Phase of Stroke in a Cynomolgus Monkey Model of Induced Cerebral Ischemia

“…Deletion of the MAOB gene was nonprotectivein fact, detrimentalin a mouse MCAO model; additional evidence has been obtained using a cryolesion induced model of brain injury. While reactive astrocytosis has been observed along with a prominent increase in MAOB expression, its selective inhibition had no effect on the expression of cell death and inflammation-related genes, nor did it improve the motor impairment of cryolesioned mice . The observation of upregulated MAOB in the LIV group suggests a neuroprotective role.…”

“…While reactive astrocytosis has been observed along with a prominent increase in MAOB expression, its selective inhibition had no effect on the expression of cell death and inflammation-related genes, nor did it improve the motor impairment of cryolesioned mice. 118 The observation of upregulated MAOB in the LIV group suggests a neuroprotective role. The giant phosphoprotein AHNAK is expressed in several cell types, including reactive astrocytes, and implicated in a variety of cellular processes.…”