Reversal of Impaired Hippocampal Long-Term Potentiation and Contextual Fear Memory Deficits in Angelman Syndrome Model Mice by ErbB Inhibitors

Hanoch Kaphzan; Pepe Hernandez; Joo In Jung; Kiriana K Cowansage; Katrin Deinhardt; Moses V Chao; Ted Abel; Eric Klann

doi:10.1016/j.biopsych.2012.01.021

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Reversal of Impaired Hippocampal Long-Term Potentiation and Contextual Fear Memory Deficits in Angelman Syndrome Model Mice by ErbB Inhibitors

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Reversal of Impaired Hippocampal Long-Term Potentiation and Contextual Fear Memory Deficits in Angelman Syndrome Model Mice by ErbB Inhibitors

Hanoch Kaphzan, Pepe Hernandez, Joo In Jung, Kiriana K Cowansage, Katrin Deinhardt, Moses V Chao, Ted Abel and Eric Klann

Biological psychiatry (1969), Vol.72(3), pp.182-190

08/01/2012

DOI: 10.1016/j.biopsych.2012.01.021

PMCID: PMC3368039

PMID: 22381732

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Abstract

Angelman syndrome (AS) is a human neuropsychiatric disorder associated with autism, mental retardation, motor abnormalities, and epilepsy. In most cases, AS is caused by the deletion of the maternal copy of UBE3A gene, which encodes the enzyme ubiquitin ligase E3A, also termed E6-AP. A mouse model of AS has been generated and these mice exhibit many of the observed neurological alterations in humans. Because of clinical and neuroanatomical similarities between AS and schizophrenia, we examined AS model mice for alterations in the neuregulin-ErbB4 pathway, which has been implicated in the pathophysiology of schizophrenia. We focused our studies on the hippocampus, one of the major brain loci impaired in AS mice. We determined the expression of neuregulin 1 and ErbB4 receptors in AS mice and wild-type littermates (ages 10–16 weeks) and studied the effects of ErbB inhibition on long-term potentiation in hippocampal area cornu ammonis 1 and on hippocampus-dependent contextual fear memory. We observed enhanced neuregulin-ErbB4 signaling in the hippocampus of AS model mice and found that ErbB inhibitors could reverse deficits in long-term potentiation, a cellular substrate for learning and memory. In addition, we found that an ErbB inhibitor enhanced long-term contextual fear memory in AS model mice. Our findings suggest that neuregulin-ErbB4 signaling is involved in synaptic plasticity and memory impairments in AS model mice, suggesting that ErbB inhibitors have therapeutic potential for the treatment of AS.

LTP

Angelman syndrome

NRG1

hippocampus

ErbB4

interneurons

Details

Title: Subtitle: Reversal of Impaired Hippocampal Long-Term Potentiation and Contextual Fear Memory Deficits in Angelman Syndrome Model Mice by ErbB Inhibitors
Creators: Hanoch Kaphzan - Center for Neural Science, New York University, New York, New York
Pepe Hernandez - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania
Joo In Jung - Center for Neural Science, New York University, New York, New York
Kiriana K Cowansage - Center for Neural Science, New York University, New York, New York
Katrin Deinhardt - Departments of Cell Biology, Physiology and Neuroscience, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York
Moses V Chao - Departments of Cell Biology, Physiology and Neuroscience, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York
Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania
Eric Klann - Center for Neural Science, New York University, New York, New York
Resource Type: Journal article
Publication Details: Biological psychiatry (1969), Vol.72(3), pp.182-190
DOI: 10.1016/j.biopsych.2012.01.021
PMID: 22381732
PMCID: PMC3368039
NLM abbreviation: Biol Psychiatry
ISSN: 0006-3223
eISSN: 1873-2402
Publisher: Elsevier Inc
Language: English
Date published: 08/01/2012
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065828102771

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