Speaker：Jiali Duan（段佳丽）, Can Liu（刘灿）, Jiaqian Li (李佳芊), Yifei Weng（翁翊菲）, Siyang Li（李思扬）

Abstract:

ASD (Autism Spectrum Disorder) is a developmental disorder which affects about 1% people in the world. The core symptoms include difficulties with social interaction and restricted repetitive behaviors. ASD is lifelong and cannot be cured. People have done a lot of work to elucidate the causes of ASD including psychology, genetics, neuroscience and so on, but so far it has not been fully understood. In this JC, we focus on one gene, shank3. We’ll talk about how this gene is studied and use this gene as an example to discuss the difficulties on the study of ASD.

ASD was thought as an acquired disease for a long time. After some studies on twins and pedigrees, genetic factors of ASD were first considered and taken seriously. Scientists sought for the possible genes related to ASD by various means after they found some  chromosomal abberations on ASD patients. Now we could focus on specific genes to study deeply on ASD.

Disruption of Shank3 gene is thought to be associated with autism in some cases according to many genetic researches. To elucidate its neurological basis and circuitry mechanism, proper animal models are required. In main paper 1, mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice.

After the SHANK3 mutant mouse model obtained, researchers can try to figure out its disease mechanism and rescue strategy. In this novel paper (Qin 2018), they found an innovative treatment strategy that would effectively rescue social deficiency. HDAC inhibition via Romidepsin could knock down HDAC’s overexpression caused by β-catenin’s nuclear localization. This inhibition would stimulate the expression of actin regulators and NMDAR, eventually leads to restored membrane localization of NMDAR at the post-synaptic membrane of PFC, and rescues the social deficit of the mouse model.

Although ASD can not be cured, patients with ASD still have opportunities to live independently and return society by specific education. Now, we can use ADI-R and ADOS to diagnose ASD. In addition, we can try to improve patients social communication by educational intervening, including Applied Behavior Analysis(ABA), Structure Teaching and so on. Since, we don't have specific medicine to cure ASD, scientists try to design drug after well understanding causes of ASD and make many efforts to diagnose ASD patients earlier by sequencing and other behavioral research, including eye movement experiment.

Guest information:

1. Dr. Rong Zhang

http://nri.bjmu.edu.cn/ktzjj/44189.htm

2. Dr. Yulong Li (PKU)

http://www.bio.pku.edu.cn/teacher_dis_oa.php?cid=146&&teaid=43

Recommend Literatures：

Review:

Miles, J. H. "Autism spectrum disorders--a genetics review. " Genetics in Medicine Official Journal of the American College of Medical Genetics 13.4(2011):278.

Link：https://www.nature.com/articles/gim9201151

Papers:

1. Peça, João, et al. "Shank3 mutant mice display autistic-like behaviours and striatal dysfunction." Nature 472.7344(2011):437.

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090611/

2. Qin, L., et al. "Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition." Nature Neuroscience 21.4(2018):564-575.

Link: https://www.nature.com/articles/s41593-018-0110-8