PMID- 28500650
OWN - NLM
STAT- MEDLINE
DCOM- 20180202
LR  - 20191210
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Linking)
VI  - 27
IP  - 8
DP  - 2017 Aug
TI  - Aberrant cognitive phenotypes and altered hippocampal BDNF expression related to 
      epigenetic modifications in mice lacking the post-synaptic scaffolding protein 
      SHANK1: Implications for autism spectrum disorder.
PG  - 906-919
LID - 10.1002/hipo.22741 [doi]
AB  - Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders 
      characterized by persistent deficits in social communication/interaction, 
      together with restricted/repetitive patterns of behavior. ASD is among the most 
      heritable neuropsychiatric conditions, and while available evidence points to a 
      complex set of genetic factors, the SHANK gene family has emerged as one of the 
      most promising candidates. Here, we assessed ASD-related phenotypes with 
      particular emphasis on social behavior and cognition in Shank1 mouse mutants in 
      comparison to heterozygous and wildtype littermate controls across development in 
      both sexes. While social approach behavior was evident in all experimental 
      conditions and social recognition was only mildly affected by genotype, 
      Shank1(-/-) null mutant mice were severely impaired in object recognition memory. 
      This effect was particularly prominent in juveniles, not due to impairments in 
      object discrimination, and replicated in independent mouse cohorts. At the 
      neurobiological level, object recognition deficits were paralleled by increased 
      brain-derived neurotrophic factor (BDNF) protein expression in the hippocampus of 
      Shank1(-/-) mice; yet BDNF levels did not differ under baseline conditions. We 
      therefore investigated changes in the epigenetic regulation of hippocampal BDNF 
      expression and detected an enrichment of histone H3 acetylation at the Bdnf 
      promoter1 in Shank1(-/-) mice, consistent with increased learning-associated 
      BDNF. Together, our findings indicate that Shank1 deletions lead to an aberrant 
      cognitive phenotype characterized by severe impairments in object recognition 
      memory and increased hippocampal BDNF levels, possibly due to epigenetic 
      modifications. This result supports the link between ASD and intellectual 
      disability, and suggests epigenetic regulation as a potential therapeutic target.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Sungur, A Ozge
AU  - Sungur AO
AD  - Behavioral Neuroscience, Experimental and Biological Psychology, 
      Philipps-University of Marburg, Marburg, Germany.
FAU - Jochner, Magdalena C E
AU  - Jochner MCE
AD  - Behavioral Neuroscience, Experimental and Biological Psychology, 
      Philipps-University of Marburg, Marburg, Germany.
FAU - Harb, Hani
AU  - Harb H
AD  - Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, 
      Philipps-University of Marburg, Marburg, Germany.
FAU - Kilic, Ayse
AU  - Kilic A
AD  - Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, 
      Philipps-University of Marburg, Marburg, Germany.
FAU - Garn, Holger
AU  - Garn H
AD  - Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, 
      Philipps-University of Marburg, Marburg, Germany.
FAU - Schwarting, Rainer K W
AU  - Schwarting RKW
AD  - Behavioral Neuroscience, Experimental and Biological Psychology, 
      Philipps-University of Marburg, Marburg, Germany.
FAU - Wohr, Markus
AU  - Wohr M
AUID- ORCID: 0000-0001-6986-5684
AD  - Behavioral Neuroscience, Experimental and Biological Psychology, 
      Philipps-University of Marburg, Marburg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20170529
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (SHANK1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - *Autism Spectrum Disorder/complications/genetics/metabolism/pathology
MH  - Body Weight/genetics
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cognition Disorders/*etiology/genetics
MH  - Discrimination, Psychological/physiology
MH  - Disease Models, Animal
MH  - Epigenesis, Genetic/*genetics
MH  - Hippocampus/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/*deficiency/genetics/metabolism
MH  - Phenotype
MH  - Recognition, Psychology/physiology
MH  - Social Behavior
MH  - Vocalization, Animal/physiology
OTO - NOTNLM
OT  - acetylation
OT  - hippocampus
OT  - novel object recognition
OT  - social approach
OT  - social recognition
EDAT- 2017/05/14 06:00
MHDA- 2018/02/03 06:00
CRDT- 2017/05/14 06:00
PHST- 2017/02/13 00:00 [received]
PHST- 2017/04/05 00:00 [revised]
PHST- 2017/05/03 00:00 [accepted]
PHST- 2017/05/14 06:00 [pubmed]
PHST- 2018/02/03 06:00 [medline]
PHST- 2017/05/14 06:00 [entrez]
AID - 10.1002/hipo.22741 [doi]
PST - ppublish
SO  - Hippocampus. 2017 Aug;27(8):906-919. doi: 10.1002/hipo.22741. Epub 2017 May 29.