title: Altered cerebellar organization and function in monoamine oxidase A hypomorphic mice.
abstract: 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.
authors.affiliation: Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Loai
authors.initials: L
authors.lastname: Alzghoul
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
authors.forename: Foteini
authors.initials: F
authors.lastname: Delis
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Darling
authors.forename: Sean C
authors.initials: SC
authors.lastname: Godar
authors.forename: Junlin
authors.initials: J
authors.lastname: Zhang
authors.forename: Samuel
authors.initials: S
authors.lastname: Grant
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Simpson
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Rick C S
authors.initials: RC
authors.lastname: Lin
authors.forename: Jean C
authors.initials: JC
authors.lastname: Shih
mesh_terms: D000818:Animals; D064026:Calbindins; D002452:Cell Count; D002531:Cerebellum / Q000378:metabolism / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D005684:Gait / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology*; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology; D045442:Rotarod Performance Test; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
chemical_list: D064026:Calbindins; D064030:S100 Calcium Binding Protein G; D008995:Monoamine Oxidase