Maob-flox Mouse

Maob, short for Monoamine oxidase B, is a mitochondrial enzyme that degrades biogenic and dietary monoamines. It is involved in the synthesis of GABA and hydrogen peroxide in astrocytes, and its activity impacts the regulation of dopaminergic neuronal activity [1,3]. In addition, it is associated with processes like extracellular matrix remodeling and cytokine signaling in the context of cancer microenvironments [2].

A Maob conditional knockout (cKO) mouse line was generated to study the role of astrocytic Maob. In this model, Maob ablation led to a significant reduction in GABA immunoreactivity in striatal astrocytes and cerebellar glial cells. Also, tonic GABA currents from granule cells and medium spiny neurons were substantially decreased, validating that astrocytic Maob is crucial for GABA synthesis in astrocytes [3].

In the context of Parkinson's disease, Maob in reactive astrocytes mediates the aberrant synthesis of GABA and hydrogen peroxide, which suppresses dopaminergic neuronal activity and contributes to neuronal death. Reversible Maob inhibitors can reduce reactive astrogliosis and restore dopaminergic neuronal activity in rodent models [1].

In prostate cancer, knockdown of Maob in human prostate stromal fibroblasts restricted the proliferation, migration, and invasion of co-cultured PC cells and the growth of co-inoculated prostate tumors in mice. Pharmacological inhibition of stromal Maob also restricted PC xenograft growth in mice [2].

In conclusion, Maob plays essential roles in neurotransmitter regulation, especially in the context of dopaminergic neuron function in Parkinson's disease, and in prostate cancer growth and progression. The Maob cKO mouse model has been instrumental in revealing its role in astrocytic GABA synthesis, and these findings have implications for understanding and treating related diseases.