Social memory, amnesia, and autism: Brain oxytocin secretion is regulated by NAD + metabolites and single nucleotide polymorphisms of CD38
| Autor: | Toshio Munesue, Shirin Akther, Wen-Jie Ma, Yoshio Minabe, Chiharu Higashida, Haruhiro Higashida, Jian-Jun Huang, Mitsuru Kikuchi, Shigeru Yokoyama, Li Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Proband
medicine.medical_specialty genetic structures Vasopressins Autism Amnesia Single-nucleotide polymorphism Biology Oxytocin Irritability Polymorphism Single Nucleotide behavioral disciplines and activities Oxytocin secretion Mice Cellular and Molecular Neuroscience Memory Internal medicine mental disorders medicine Animals Humans Social behavior Autistic Disorder Allele ADP-ribosyl Cyclase Administration Intranasal Mice Knockout Genetics cADPR TRPM2 channels Brain Exons Cell Biology NAD medicine.disease ADP-ribosyl Cyclase 1 Introns Endocrinology medicine.symptom Cyclase activity CD38 |
| Zdroj: | Neurochemistry International. 61(6):828-838 |
| ISSN: | 0197-0186 |
| Popis: | Previously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase activity, plays a critical role in mouse social behavior by regulating the release of oxytocin (OXT), which is essential for mutual recognition. When CD38 was disrupted, social amnesia was observed in Cd38 knockout mice. The autism spectrum disorders (ASDs), characterized by defects in reciprocal social interaction and communication, occur either sporadically or in a familial pattern. However, the etiology of ASDs remains largely unknown. Therefore, the theoretical basis for pharmacological treatments has not been established. Hence, there is a rationale for investigating single nucleotide polymorphisms (SNPs) in the human CD38 gene in ASD subjects. We found several SNPs in this gene. The SNP rs3796863 (C > A) was associated with high-functioning autism (HFA) in American samples from the Autism Gene Resource Exchange. Although this finding was partially confirmed in low-functioning autism subjects in Israel, it has not been replicated in Japanese HFA subjects. The second SNP of interest, rs1800561 (4693C > T), leads to the substitution of an arginine (R) at codon 140 by tryptophan (W; R140W) in CD38. This mutation was found in four probands of ASD and in family members of three pedigrees with variable levels of ASD or ASD traits. The plasma levels of OXT in ASD subjects with the R140W allele were lower than those in ASD subjects lacking this allele. The OXT levels were unchanged in healthy subjects with or without this mutation. One proband with the R140W allele receiving intranasal OXT for approximately 3 years showed improvement in areas of social approach, eye contact and communication behaviors, emotion, irritability, and aggression. Five other ASD subjects with mental deficits received nasal OXT for various periods; three subjects showed improved symptoms, while two showed little or no effect. These results suggest that SNPs in CD38 may be possible risk factors for ASD by abrogating OXT function and that some ASD subjects can be treated with OXT in preliminary clinical trials. © 2011 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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