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Brain Sci. 2017, 7(10), 132;

Effects of Three Lipidated Oxytocin Analogs on Behavioral Deficits in CD38 Knockout Mice

Department of Basic Research on Social Recognition, Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan
Faculty of Pharmaceutical Sciences, Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan
Departments of Biochemistry and Molecular Vascular Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan
Author to whom correspondence should be addressed.
Received: 14 September 2017 / Revised: 3 October 2017 / Accepted: 11 October 2017 / Published: 16 October 2017
(This article belongs to the Special Issue Autism Spectrum Disorder: From Etio-Pathology to Treatment)
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Oxytocin (OT) is a nonapeptide that plays an important role in social behavior. Nasal administration of OT has been shown to improve trust in healthy humans and social interaction in autistic subjects. As is consistent with the nature of a peptide, OT has some unfavorable characteristics: it has a short half-life in plasma and shows poor permeability across the blood-brain barrier. Analogs with long-lasting effects may overcome these drawbacks. To this end, we have synthesized three analogs: lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated to the cysteine and tyrosine residues, lipo-oxytocin-2 (LOT-2) and lipo-oxytocin-3 (LOT-3), which include one palmitoyl group conjugated at the cysteine or tyrosine residue, respectively. The following behavioral deficits were observed in CD38 knockout (CD38−/−) mice: a lack of paternal nurturing in CD38−/− sires, decreased ability for social recognition, and decreased sucrose consumption. OT demonstrated the ability to recover these disturbances to the level of wild-type mice for 30 min after injection. LOT-2 and LOT-3 partially recovered the behaviors for a short period. Conversely, LOT-1 restored the behavioral parameters, not for 30 min, but for 24 h. These data suggest that the lipidation of OT has some therapeutic benefits, and LOT-1 would be most useful because of its long-last activity. View Full-Text
Keywords: oxytocin; autism; CD38; lipidation; social behaviors oxytocin; autism; CD38; lipidation; social behaviors

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Cherepanov, S.M.; Akther, S.; Nishimura, T.; Shabalova, A.A.; Mizuno, A.; Ichinose, W.; Shuto, S.; Yamamoto, Y.; Yokoyama, S.; Higashida, H. Effects of Three Lipidated Oxytocin Analogs on Behavioral Deficits in CD38 Knockout Mice. Brain Sci. 2017, 7, 132.

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