PMID- 23201251 OWN - NLM STAT- MEDLINE DCOM- 20150714 LR - 20211021 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 232 DP - 2013 Mar 1 TI - VMAT1 deletion causes neuronal loss in the hippocampus and neurocognitive deficits in spatial discrimination. PG - 32-44 LID - S0306-4522(12)01134-7 [pii] LID - 10.1016/j.neuroscience.2012.11.023 [doi] AB - 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. CI - Copyright (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Multani, P K AU - Multani PK AD - Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA. FAU - Hodge, R AU - Hodge R AD - Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA. FAU - Estevez, M A AU - Estevez MA AD - Department of Biology, University of Pennsylvania, Philadelphia, PA, USA. FAU - Abel, T AU - Abel T AD - 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. FAU - Kung, H AU - Kung H AD - Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. FAU - Alter, M AU - Alter M AD - Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA. FAU - Brookshire, B AU - Brookshire B AD - Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA. FAU - Lucki, I AU - Lucki I AD - 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. FAU - Nall, A H AU - Nall AH AD - Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA. FAU - Talbot, K AU - Talbot K AD - Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA. FAU - Doyle, G A AU - Doyle GA AD - Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Translational Research Laboratories, Philadelphia, PA, USA. FAU - Lohoff, F W AU - Lohoff FW AD - 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. LA - eng GR - R01MH86599/MH/NIMH NIH HHS/United States GR - K08MH080372/MH/NIMH NIH HHS/United States GR - K08 MH080372/MH/NIMH NIH HHS/United States GR - T32MH14654/MH/NIMH NIH HHS/United States GR - R01 MH086599/MH/NIMH NIH HHS/United States GR - T32 MH014654/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20121129 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (RNA, Messenger) RN - 0 (Slc18a1 protein, mouse) RN - 0 (Slc18a2 protein, mouse) RN - 0 (Synaptophysin) RN - 0 (Syp protein, mouse) RN - 0 (Vesicular Monoamine Transport Proteins) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis/physiology MH - Brain/pathology/*physiopathology MH - Caspase 3/metabolism MH - Cognition Disorders/pathology/*physiopathology MH - Conditioning, Psychological/physiology MH - Discrimination, Psychological/*physiology MH - Fear/physiology MH - Male MH - Mice, Knockout MH - Neurogenesis/physiology MH - Neurons/*pathology/physiology MH - RNA, Messenger/metabolism MH - Recognition, Psychology/physiology MH - Space Perception/*physiology MH - Synaptophysin/metabolism MH - Vesicular Monoamine Transport Proteins/*deficiency/genetics/metabolism PMC - PMC4364608 MID - NIHMS436832 EDAT- 2012/12/04 06:00 MHDA- 2015/07/15 06:00 PMCR- 2015/03/18 CRDT- 2012/12/04 06:00 PHST- 2012/09/21 00:00 [received] PHST- 2012/11/06 00:00 [revised] PHST- 2012/11/07 00:00 [accepted] PHST- 2012/12/04 06:00 [entrez] PHST- 2012/12/04 06:00 [pubmed] PHST- 2015/07/15 06:00 [medline] PHST- 2015/03/18 00:00 [pmc-release] AID - S0306-4522(12)01134-7 [pii] AID - 10.1016/j.neuroscience.2012.11.023 [doi] PST - ppublish SO - Neuroscience. 2013 Mar 1;232:32-44. doi: 10.1016/j.neuroscience.2012.11.023. Epub 2012 Nov 29.