Sanbing Shen

University of Aberdeen, UK

Abstract

[O11] Roles of the PAC1 receptor in mouse neurogenesis

Sanbing Shen, Bing Lang, and Colin D. MiCaig; University of Aberdeen, UK

The pituitary adenylate cyclase activating polypeptide (PACAP) and its high affinity receptor PAC1 are encoded by genes ADCYAP1 and ADCYAP1R1, respectively. They are highly expressed in the embryonic and adult central nervous system, and are recently implicated in the Japanese schizophrenic population. However, it is not known whether expression of the ADCYAP1 or ADCYAP1R1 is altered in schizophrenia. We have investigated roles of the PAC1 receptor through the gain-of-function approach, by over-expressing the human PAC1 receptor with a 130 kb transgene in mice. Transgenic mice develop transgene dose-dependent enlargement of the ventricles, and reduction of the cerebral cortex and corpus callosum. These neuroanatomical changes are commonly found in hydrocephalus and schizophrenia, and the defects are associated with reduced neural proliferation and increased neuronal apoptosis during embryonic neurogenesis. PAC1 receptor is also expressed in mammalian retina and involved in processing light information. We demonstrate that PACAP signaling plays an important role in the development of retina, particularly in the genesis of GABAergic amacrine cells. Overexpression of the PAC1 receptor leads to an early exit from retinal proliferation, reduced production of GABAergic neurons, and a marked decline in visual function. Possible involvement of PACAP signaling in choroid plexus, CSF flow, hippocampal formation and adult neurogenesis will also be discussed.

Biography

Sanbing Shen graduated from Hangzhou University in 1983 and received MSc from the Institute of Developmental Biology (Beijing) in 1986. He did his PhD at Hubrecht Laboratory (Utrecht) in 1993 on retinoic acid receptors. Following further training on manipulations of large DNA molecules at MRC HGU (Edinburgh), he worked at MRC BMU (Edinburgh) on serotonin transporter and G-protein coupled receptors (VPAC2 and PAC1) for neuropeptides VIP and PACAP, via gain and loss of function in mice.  Shen joined the University of Aberdeen in 2002 as a Lecturer, worked on neurodevelopment and stem cells, and became a Senior Lecturer in 2007.