Title: Haploinsufficiency of the autism candidate gene Neurobeachin induces autism-like behaviors and affects cellular and molecular processes of synaptic plasticity in mice
Authors: Nuytens, Kim * ×
Gantois, Ilse *
Stijnen, Pieter
Iscru, Emilia
Laeremans, Annelies
Serneels, Lutgarde
Van Eylen, Lien
Liebhaber, Stephen A
Devriendt, Koenraad
Balschun, Detlef
Arckens, Lut
Creemers, John
D'Hooge, Rudi #
Issue Date: Mar-2013
Publisher: Blackwell Science
Series Title: Neurobiology of Disease vol:51 pages:144-151
Abstract: Neurobeachin (NBEA), a brain-enriched multidomain scaffolding protein involved in neurotransmitter release and synaptic functioning, has been identified as a candidate gene for autism spectrum disorder (ASD) in four unrelated patients haploinsufficient for NBEA. The aim of this study was to map the behavioral phenotype of Nbea(+/-) mice in order to understand its contribution to the pathogenesis of ASD. ASD-like behavioral variables of Nbea(+/-) mice were related to basal neuronal activity in different brain regions by in situ hybridizations and extracellular field recordings of synaptic plasticity in hippocampal cornu ammonis 1 (CA1) region. Levels of BDNF and phosphorylated cAMP response element-binding protein (CREB) were measured in an attempt to investigate putatively underlying changes in these neuromolecules. Nbea(+/-) mice exhibit several ASD-like features, including changes in self-grooming behavior, social behaviors, conditioned fear responses, and spatial learning and memory, which coincided with enhanced long-term potentiation (LTP) in their CA1 region. The observed alterations in learning and memory and hippocampal LTP are concomitant with decreased expression of the immediate early gene zif268 in dorsomedial stratiatum and hippocampal CA1 region, increased CREB phosphorylation, and increased hippocampal BDNF expression. These findings indicate that Nbea haploinsufficiency leads to various molecular and cellular changes that affect neuroplasticity and behavioral functions in mice, and could thus underlie the ASD symptomatology in NBEA deficient humans.
ISSN: 0969-9961
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biochemical Neuroendocrinology
Laboratory for Biological Psychology
Department of Human Genetics - miscellaneous
* (joint) first author
× corresponding author
# (joint) last author

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