differential neuregulin 1 cleavage in the prefrontal cortex and hippocampus in schizophrenia and bipolar disorder preliminary findings调节微分1乳沟在前额叶皮层和海马在精神分裂症和双相情感障碍的初步研究结果.pdfVIP

Differential Neuregulin 1 Cleavage in the Prefrontal Cortex and Hippocampus in Schizophrenia and Bipolar Disorder: Preliminary Findings 1,3 2 2 3 Ketan Marballi , Dianne Cruz , Peter Thompson , Consuelo Walss-Bass * 1 University of Texas Health Science Center at San Antonio, Department of Cellular and Structural Biology, San Antonio, Texas, United States of America, 2 Southwest Brain Bank, Depa rt ment of Psyc hiat ry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America, 3 Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America Abstract Background: Neuregulin 1 (NRG1) is a key candidate susceptibility gene for both schizophrenia (SCZ) and bipolar disorder (BPD). The function of the NRG1 transmembrane proteins is regulated by cleavage. Alteration of membrane bound-NRG1 cleavage has been previously shown to be associated with behavioral impairments in mouse models lacking expression of NRG1-cleavage enzymes such as BACE1 and gamma secretase. We sought to determine whether alterations in NRG1 cleavage and associated enzymes occur in patients with SCZ and BPD. Methodology/Principal Findings: Using human postmortem brain, we evaluated protein expression of NRG1 cleavage products and enzymes that cleave at the external (BACE1, ADAM17, ADAM19) and internal (PS1-gamma secretase) sides of the cell membrane. We used three different cohorts (Controls, SCZ and BPD) and two distinct brain regions: BA9-prefrontal cortex (Controls (n = 6), SCZ (n = 6) and BPD (n = 6)) and hippocampus (Controls (n = 5), SCZ (n = 6) and BPD (n = 6))