05 Nov2021

Exploring the “brave new world”: from psychology to brain and mind research to neuropsychiatric dis

Exploring the “brave new world”: from psychology to brain and mind research to neuropsychiatric disorders

Wen-Sung Lai (賴文崧)  

1. Laboratory of Integrated Neuroscience and Ethology (LINE), Department of  Psychology, National Taiwan University, Taipei, Taiwan 

2. Department of Psychology, National Taiwan University, Taipei, Taiwan 3. Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei,  Taiwan 

4. Neurobiology and Cognitive Science Center, National Taiwan University, Taipei,  Taiwan 

As we know that the study of the mind and brain has often been calledThe last  frontier of science.Indeed, brain is one of the largest and most complex organs in  the human body. The goal of my lab, Laboratory of Integrated Neuroscience and  Ethology (LINE), aims at studying brain and mind from multidisciplinary approaches.  We also formed joint forces to investigate neuropsychiatric disorders from basics to  clinics and develop novel therapeutic targets for the treatment of these disorders,  including schizophrenia. Schizophrenia is a severe mental illness that affects 1% of  population worldwide. Regardless of numerous adverse effects, current available  antipsychotics have been mainly focused on positive symptoms. The treatment of  negative symptoms and cognitive deficits of schizophrenia has become an unmet  medical need for antipsychotics development. A selection of potential therapeutic  compounds was evaluated and examined. First, in agreement with clinical practice,  we demonstrated the therapeutic potential of lithium in the treatment of  schizophrenia-related deficits and the involvement of the AKT1-GSK3 signaling  pathway. Furthermore, given that NMDAR-mediated signaling pathway has been  implicated in cognitive functions, we investigated the therapeutic effect of  NMDA-enhancing agents and their underlying mechanisms. We found that sarcosine  effectively regulated surface trafficking of NMDARs, NMDAR-evoked  electrophysiological activity, brain glycine levels, and MK-801-induced abnormalities  in the brain, which contributed to the amelioration of schizophrenia-related symptoms.  We further demonstrated the therapeutic potentials of RS-D7 (a new chemical entity)  in the treatment of negative/cognition symptoms of schizophrenia and other  neuropsychiatric disorders, including multiple system atrophy (MSA, a progressive  neurodegenerative disorder). In addition, the recent development and advances in  human 3D brain organoid (also called mini-brain) opens a promising avenue to

understand the basics of the brain and advance precision-medicine drug development.  Taking advantage of 3D brain organoids, we currently aim at untangling the mystery  of brain development in Prader-Willi syndrome (PWS) and developing a new  high-throughput screening platform for precision medicine. We look forward to  building up further collaboration with you all for developing new pharmaceutical  agents to treat unmet medical needs in the near future. 

Keywords: Laboratory of Integrated Neuroscience and Ethology (LINE),  neuropsychiatric disorders, schizophrenia, animal models, unmet medical need, drug  development, AKT1, NMDA receptor, drug candidate, multiple system atrophy (MSA), brain organoids, Prader-Willi syndrome (PWS)