Priority CommunicationReversal of Impaired Hippocampal Long-Term Potentiation and Contextual Fear Memory Deficits in Angelman Syndrome Model Mice by ErbB Inhibitors
Section snippets
Mice
Angelman syndrome model mice were generated and genotyped using specific primers as described previously (10). For details regarding mice, see Supplement 1 Methods.
Tissue Preparation, Immunoprecipitation, and Western Blots
Angelman syndrome mice and wild-type littermates were decapitated; the brain was quickly extracted; and hippocampi from both hemispheres were removed, tissue was prepared, and Western blots were performed using standard protocols. For details concerning homogenization buffers, immunoprecipitation, Western blot procedures, and sources
Altered Expression of NRG1 and ErbB4 in AS Model Mice
Because of several similarities between AS and schizophrenia (Table S1 in Supplement 1) and previous studies linking the NRG1-ErbB4 signaling pathway to the pathophysiology of schizophrenia, we examined NRG1 and ErbB4 expression, as well as ErbB4 phosphorylation in the hippocampus of AS model mice. Specifically, we examined NRG1 type I and type II protein levels (23) because its messenger RNA is present in large quantities in all hippocampal subregions (24). We observed a significant increase
Discussion
The involvement of NRG1-ErbB4 signaling pathway in schizophrenia has been well documented (18, 19, 20, 21). Due to several shared features between schizophrenia and AS (Table S1 in Supplement 1) and a possible genetic linkage of UBE3A gene to schizophrenia (22), we hypothesized that NRG1-ErbB4 signaling is involved in the pathophysiology of AS. We found that NRG1 levels and ErbB4 phosphorylation on two tyrosine residues were significantly increased (Figure 1A, B), whereas total ErbB4 levels
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