Case Report
An Attempt of Non-human Primate Modeling of Schizophrenia with Neonatal Challenges of Epidermal Growth Factor
Miwako Sakai1,2, Masafumi Kashiwahara3, Akiyoshi Kakita4 and Hiroyuki Nawa1*1 Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
2 Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 951-8510, Niigata, Japan
3 Shin Nippon Biomedical Laboratories, Ltd., Miyanoura, Kagoshima 981-1394, Japan
4 Department of Pathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan
- *Corresponding Author:
- Hiroyuki Nawa
Department of Molecular Biology
Brain Research Institute Niigata University
Asahimachi-dori 1-757
Niigata 951-8585, Japan
E-mail: hnawa@bri.niigata-u.ac.jp
Received date: December 17, 2013; Accepted date: January 24, 2014; Published date: January 31, 2014
Citation: Sakai M, Kashiwahara M, Kakita A, Nawa H (2014) An Attempt of Nonhuman Primate Modeling of Schizophrenia with Neonatal Challenges of Epidermal Growth Factor. J Addict Res Ther 5:170. doi: 10.4172/2155-6105.1000170
Copyright: © 2014 Sakai M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Inflammatory cytokines are implicated in the neurodevelopmental hypothesis for schizophrenia. Based on this hypothesis, we studied the establsihment of rodent models for schizophrenia by subcutaneously challenging rat or mouse neonates with various cytokines. Because of the physical and behavioral difference between animal species; however, it is difficult to fully evaluate the appropriateness of rodent models. To overcome this problem, we attempted to establish a non-human primate model of schizophrenia. We subcutaneously injected epidermal growth factor (EGF: 0.3 mg/kg/day) to 3 male neonatal cynomolgus monkeys for a total of 7 or 9 days from 14 days of age. During the following 4 or 5 years, no abnormal behaviors were observed in these monkeys treated with EGF; however, at the age of 6 years, 1 monkey exhibited abnormal behavioral traits: stereotypic movement, vocalization, alert motion, and self injury. It was noteworthy that the monkey often showed agitation and clapped its hands over its eyes and bit his hands in periods of illumination, although not under darkened conditions. The behavioral abnormalities except vocalization were ameliorated by 10-day oral treatment with risperidone at 0.10 mg/kg/day. Although this study needs to be replicated, this case report suggests the possibility that hyper EGF signals at the perinatal stage of non-human primates result in post-pubertal behavioral/cognitive deficits, which possibly imitate some pathological features of human schizophrenia.
