Exploring the “brave new world”: from psychology to brain and mind research to neuropsychiatric disorders
Wen-Sung Lai (賴文崧)
- Laboratory of Integrated Neuroscience and Ethology (LINE), Department of Psychology, National Taiwan University, Taipei, Taiwan
- Department of Psychology, National Taiwan University, Taipei, Taiwan 3. Graduate Institute of Brain and Mind Sciences, National Taiwan University, Taipei, Taiwan
- Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan
As we know that the study of the mind and brain has often been called“The 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)