Summary of medical doctoral thesis: Research on establishing an autism model using sodium valproate and ameliorative effects of enriched environment on behaviors in white mice

This research with two aims: Establishing an animal model of autism using Swiss white mice by prenatal exposure to sodium valproate. Evaluating the effects of enriched environment on behaviors in modelled white mice
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Summary of medical doctoral thesis: Research on establishing an autism model using sodium valproate and ameliorative effects of enriched environment on behaviors in white mice MINISTRY OF MINISTRY OF DEFENCEEDUCATION AND TRAINING VIETNAM MILITARY MEDICAL UNIVERSITY DAO THU HONGRESEARCH ON ESTABLISHING AN AUTISM MODEL USINGSODIUM VALPROATE AND AMELIORATIVE EFFECTS OF ENRICHED ENVIRONMENT ON BEHAVIORS IN WHITE MICE Speciality: Physiology Code: 62720107 SUMMARY OF MEDICAL DOCTORAL THESIS HANOI - 2018 This research was carried out in Vietnam Military Medical UniversitySupervisors: 1. Tran Hai Anh, M.D., Ph.D., Assoc.Prof. 2. Can Van Mao, M.D., Ph.D., Assoc.Prof. Reviewer 1: Reviewer 2: Reviewer 3:This thesis will be defended in doctoral examination council ofVietnam Military Medical University at….on the date of……………..This thesis is available at: 1. National Library 2. Library of Vietnam Military Medical University 3. …………………………………………………. 1 INTRODUCTION1. Imperativeness Autism is a neurodevelopmental disorder whose diagnosis isbased on three behavioral criteria: unusual reciprocal socialinteractions, deficits in communication, and stereotyped repetitivebehaviors with restricted interests. The etiology and pathophysiologyof autism are unclear. Nowadays, autism is known as a modern-dayphenomenon with the prevalence increase all over the world. Thestudies of CDC shown that the prevalence of autism was 0.5 per1000 children in 1985, increased 12 per 1000 children in 2012.Prenatal exposure to valproate (VPA) leads abnormalneurodevelopment and increased risk of autism spectrum disorders.In animal model, prenatal VPA-exposure also lead abnormalbehaviors and pathology similar to that observed in autismindividuals. For that reason, valproate is used to induce animal modelof autism in order to investigate the mechanism of biological changesand to evaluate the effect of interventions for autism. In Vietnam,there are several researches about some risk factors, some clinicalfeatures in autistic patients. However, there is no research aboutanimal model of autism and pathophysiological mechanism forautism. So, we conducted this research with two aims: 1. Establishing an animal model of autism using Swiss whitemice by prenatal exposure to sodium valproate. 2. Evaluating the effects of enriched environment on behaviorsin modelled white mice.2. Scientific significance The thesis has provided data about behavioral alterations of Swissmice prenatally exposed to sodium valproate (VPA) with dose 300- 2500mg/kg i.p., creating animal model of autism in Swiss mice byusing sodium valproate i.p. at dose 500mg/kg. Providing data aboutthe ameliorating of enriched environment on behaviors in VPA-exposed mice.3. Practical significance Using that VPA-exposed mice to determine neurobiologicalalterations related to the pathogenesis of autism and assess the effectsof drugs or treatments on autism.4. Structure of the thesis The thesis consists 124 pages. 2 pages Introduction; Chapter 1(Documentary Overview) 32 pages; Chapter 2 (Subject and methods)14 pages; Chapter 3 (Results) 41 pages; Chapter 4 (Discussion) 33pages; 1 page Conclusions and 1 page Recommendations.The thesis has 22 tables (2 appendix tables), 35 figuress (5 appendixfigures) and 147 references (7 Vietnamese and 140 Englishreferences). Chapter 1. DOCUMENTARY OVERVIEW1.1. Terminology and brief history of autism Autism was first mentioned from the 1900s, derived from theGreek Autos - self, described patients with isolated, socialwithdrawal. Leo Kanner (1943) used the term autism to describe agroup of children with abnormal development such as socialinteraction deficits, impairment in language development, strangeand repetitive behaviors, early onset before 3 years of age. HansAsperger (1944) described a milder form of autism called Aspergerssyndrome. In 1960 – 1970s, several studies suggested that autismwas caused by abnormal brain structures, or by biochemical andmetabolic changes. In 1999, autism was classified as pervasivedevelopmental disorder. Accordingly, autism is a pervasive 3developmental disorder, affecting many aspects of the developmentbut the most impact on communication skills and social relations.1.2. Diagnostic criteria for autism Currently, there are two autism diagnostic criteria systems:Diagnostic and Statistical manual of Mental disorders (DSM) ofThe American Psychiatric Association and InternationalClassific ...