Altered cerebellar organization and function in monoamine oxidase A hypomorphic mice

作者：Alzghoul Loai; Bortolato Marco; Delis Foteini; Thanos Panayotis K; Darling Ryan D; Godar Sean C; Zhang Junlin; Grant Samuel; Wang Gene Jack; Simpson Kimberly L; Chen Kevin; Volkow Nora D; Lin Rick C S; Shih Jean C^*

来源：Neuropharmacology, 2012, 63(7): 1208-1217.

DOI：10.1016/j.neuropharm.2012.08.003

• Monoamine oxidase A
• Hypomorphism
• Serotonin
• Cerebellum
• Purkinje cells

Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-A(Neo)), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-A(Neo) mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO-A(Neo) mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO-A(Neo) mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum. Published by Elsevier Ltd.

• 出版日期2012-12