title: VMAT1 deletion causes neuronal loss in the hippocampus and neurocognitive deficits in spatial discrimination.
abstract: Vesicular monoamine transporters (VMAT) are involved in presynaptic storage and release of neurotransmitters. While it was thought initially that only VMAT2 is brain expressed and VMAT1 is present only in the periphery, recent data have challenged the exclusive expression of VMAT2 in the brain. To further elucidate the role of VMAT1 brain expression and its potential role in neuropsychiatric disorders, we have investigated mice lacking VMAT1. Comparison of wildtype and knock-out (KO) mice using qPCR and immunohistochemistry documents the expression of VMAT1 in the brain. Deletion of VMAT1 leads to increased hippocampal apoptosis and reduced neurogenesis as assessed by caspase-3-labeling and 5-bromo-deoxy-uridine-labeling. Behavioral data show that mice lacking VMAT1 have neurocognitive deficits. VMAT2 expression is not altered in VMAT1 KO mice, suggesting a distinct role of VMAT1. Our data support VMAT1 brain expression and suggest that VMAT1 plays a key role in survival of hippocampal neurons and thus might contribute to neurocognitive deficits observed in neuropsychiatric disorders.
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Multani
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hodge
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Estévez
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA; Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Abel
authors.affiliation: Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kung
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Alter
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Brookshire
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA; Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Lucki
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Nall
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Talbot
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Doyle
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA. Electronic address: lohoff@mail.med.upenn.edu.
authors.forename: F W
authors.initials: FW
authors.lastname: Lohoff
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000502:physiology; D004192:Discrimination, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology; D008297:Male; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000473:pathology* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology; D013028:Space Perception / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C493450:Slc18a1 protein, mouse; C493453:Slc18a2 protein, mouse; D016708:Synaptophysin; C569015:Syp protein, mouse; D050493:Vesicular Monoamine Transport Proteins; C505409:Casp3 protein, mouse; D053148:Caspase 3