Proceedings of The Physiological Society

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, PC238

Poster Communications

Role of Disrupted-in-Schizophrenia 1 (DISC1) in cortical inhibitory neurons

M. Borkowska1, J. Millar2, D. J. Porteous2, D. J. Price1

1. Centre for Integrative Physiology, The University of Edinburgh, Edinburgh, United Kingdom. 2. Medical Genetics Section, Molecular Medicine Centre, The University of Edinburgh, Edinburgh, United Kingdom.

  • Table.1 Total number of cells expressing selected interneuron markers: parvalbumin (PV), GAD67, somatostatin (STT) and calretinin (CLR); in regions of the cerebral cortex showing significant decrease in the number of parvalbumin expressing cells in L100P mice when compared to WT control (*Student's T-test; fSSp p<0.01; SSp, vAUD: p<0.05). Results presented as a mean ± SEM.

Schizophrenia is a relatively poorly understood, debilitating psychiatric disorder affecting around 0.5% of the population worldwide. Recently, it has been suggested that DISC1 might be one of the main genetic risk factors for this disease. DISC1 has been implicated in brain development, in neurite outgrowth, neural precursor proliferation/differentiation, integration of newborn neurons and neuronal migration (1). DISC1 function in radial neuronal migration has been studied in some detail but there is little evidence implicating DISC1 in tangential migration and generation of cortical interneurons. In this study, two mouse lines with point mutations in the DISC1 sequence were used: the L100P and Q31L N-ethyl-N-nitrosourea (ENU) mutant mice previously characterized as ‘schizophrenic-like' and ‘depressive-like' respectively (2). The brain tissue was collected from 21 days old mice (both sexes, 8-12g, n=4-8 of each strain and genotype). Mice were sacrificed by injecting an overdose of anaesthetic (40mg/kg sodium pentobarbital) and perfused with 10ml PBS and 5ml 4% paraformaldehyde (PFA). The brains were fixed overnight in 4% PFA, cryoprotected in 30% sucrose and cut on a Leica CM3050 S cryostat. The number and relative distribution of cortical interneuron subclasses was analysed in five 500µm wide cortical regions: frontal and barrel-field primary somatosensory (fpSS and pSS respectively), visual (Vis), ventral auditory (vAUD) and primary/ventral auditory (p/vAUD) cortices. There was a significant decrease in the number of parvalbumin positive interneurons in fpSS, pSS and vAUD cortices of L100P mice when compared to their wild-type (WT) littermates, but no reduction in the total number of interneurons (cells expressing glutamate decarboxylase GAD67) (Table.1). A minor disruption in the relative distribution of the GAD67-positive cells in pSS and vAUD cortices was observed. No such differences were observed in the Q31L line. Furthermore, there was no significant difference in the total number calretinin and somatostatin expressing interneurons in L100P mice when compared to the WT control (Table.1). These findings implicate DISC1 in the generation of particular interneuron subclasses within the cortex.

Where applicable, experiments conform with Society ethical requirements