From The Chinese Academy of Sciences [中国科学院](CN): “Researchers Reveal Novel Molecular Mechanisms underlying Onset of Autism”

From The Chinese Academy of Sciences [中国科学院](CN)

Apr 06, 2022
Editor: ZHANG Nannan

XU Zhiheng
Institute of Genetics and Developmental Biology
zhxu@genetics.ac.cn

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POSH regulates assembly of the NMDAR/PSD-95/ Shank complex and synaptic function. Image by XU Zhiheng.

Researchers led by Prof. XU Zhiheng from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, in collaboration with Prof. ZHANG Xiaohui’s Lab at Beijing Normal University [北京師範大學](CN), have revealed the important roles of the scaffold protein plenty of SH3s (POSH) in regulating the assembly of the NMDAR/PSD-95/Shank complex at the postsynaptic density. Results were published in Cell reports on April 5.

Mutations of Shank family genes are strongly associated with autism spectrum disorders (ASDs) and intellectual disability. N-methyl-D-aspartate glutamate receptor (NMDAR) dysfunction contributes to autistic-like behaviors which may be relieved by pharmacological modulation of NMDAR function. However, the molecular mechanisms involved in the regulation of Shank-mediated NMDAR function is still not clear.

In this study, the researchers found that the scaffold protein POSH clusters at excitatory synapses, together with two other scaffold proteins, PSD95 and SHANK2/3. Mice with brain specific conditional knockout (cKO) of POSH display profound autistic-like behaviors including impairments in social interactions, social communication, repetitive behaviors and deficits in learning and memory.

Combining detailed biochemical and electrophysiological analysis of POSH cKO mouse brain, they found that the normal synaptic clustering of NMDAR/PSD-95/SHANK complex is disrupted at the PSD, accompanied by the abnormal dendritic spine development and aberrant evoked NMDAR-EPSCs and NMDAR-dependent long-term potentiation in hippocampal neurons.

This study not only confirms that POSH is an ASD-associated gene, but also demonstrates that POSH is clustered in PSD with PSD-95 and SHANK2/3, and plays important roles in NMDAR-mediated transmission, spine development, and individual behaviors as well as learning and memory. It further promotes the understanding of the pathogenesis of ASD, and provides a valuable animal model for the research and treatment of ASD in the future.

This research was supported by the National Natural Science Foundation of China, and the Ministry of Science and Technology of China, etc.

See the full article here .

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The National Astronomical Observatories [国家天文台]of the Chinese Academy of Sciences [中国科学院] (NAOC) (CN) was officially founded in April 2001 through the merger of four observatories, three observing stations and one research center, all under the Chinese Academy of Sciences (CAS).

NAOC is headquartered in Beijing and has four subordinate units across the country: the Yunnan Observatory (YNAO), the Nanjing Institute of Astronomical Optics and Technology (NIAOT), the Xinjiang Astronomical Observatory (XAO) and the Changchun Observatory.

The headquarters of NAOC, located in Beijing and formerly known as the Beijing Astronomical Observatory, is simply referred to as NAOC. Established in 1958 and aiming at the forefront of astronomical science, NAOC conducts cutting-edge astronomical studies, operates major national facilities and develops state-of the-art technological innovations. Applying astronomical methods and knowledge to fulfill national interests and needs is also an integral part of the mission of NAOC. NAOC hosts the Center for Astronomical Mega-Science of Chinese Academy of Sciences (CAMS), which is a new initiative to establish a mechanism for reaching consensus in the construction of major facilities, operations and technology developments among the CAS core observatories (NAOC; the Purple Mountain Observatory, PMO; and the Shanghai Astronomical Observatory, SHAO). CAMS will strive for the sharing of financial, personnel resources and technical expertise among the three core observatories of CAS.

NAOC’s main research involves cosmological large-scale structures, the formation and evolution of galaxies and stars, high-energy astrophysics, solar magnetism and activity, lunar and deep space exploration, and astronomical instrumentation.

NAOC has seven major research divisions in the areas of optical astronomy, radio astronomy, galaxies and cosmology, space science, solar physics, lunar and deep space exploration, and applications in astronomy. These divisions encompass more than 50 research groups and house the CAS Key Laboratories of Optical Astronomy, Solar Activity, Lunar and Deep-Space Exploration, Space Astronomical Science and Technology, and Computational Astrophysics.

NAOC also has three major observing stations: Xinglong, for optical and infrared astronomy; Huairou, for solar magnetics; and Miyun, for radio astronomy and satellite data downlinks. NAOC has been deeply involved in the China Lunar Exploration Program, from designing and managing lunar exploration satellite payload systems, to receiving, storing and analyzing the data transmitted by these satellites from space. NAOC also has a GPU super-cluster computing facility with 85 nodes at a peak performance of up to 280 teraflops.

NAOC also publishes Research in Astronomy and Astrophysics (RAA), a journal catalogued by SCI.

The Chinese Academy of Sciences (CN) is the linchpin of China’s drive to explore and harness high technology and the natural sciences for the benefit of China and the world. Comprising a comprehensive research and development network, a merit-based learned society and a system of higher education, CAS brings together scientists and engineers from China and around the world to address both theoretical and applied problems using world-class scientific and management approaches.

Since its founding, CAS has fulfilled multiple roles — as a national team and a locomotive driving national technological innovation, a pioneer in supporting nationwide S&T development, a think tank delivering S&T advice and a community for training young S&T talent.

Now, as it responds to a nationwide call to put innovation at the heart of China’s development, CAS has further defined its development strategy by emphasizing greater reliance on democratic management, openness and talent in the promotion of innovative research. With the adoption of its Innovation 2020 programme in 2011, the academy has committed to delivering breakthrough science and technology, higher caliber talent and superior scientific advice. As part of the programme, CAS has also requested that each of its institutes define its “strategic niche” — based on an overall analysis of the scientific progress and trends in their own fields both in China and abroad — in order to deploy resources more efficiently and innovate more collectively.

As it builds on its proud record, CAS aims for a bright future as one of the world’s top S&T research and development organizations.