精神分裂症患者背外侧前额叶皮质中M1型毒蕈碱受体减少。

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia.

作者信息

Dean B, McLeod M, Keriakous D, McKenzie J, Scarr E

机构信息

The Rebecca L Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia.

出版信息

Mol Psychiatry. 2002;7(10):1083-91. doi: 10.1038/sj.mp.4001199.

DOI:10.1038/sj.mp.4001199

PMID:12476323

Abstract

To test the hypothesis that muscarinic receptors are involved in the pathology of schizophrenia, we measured muscarinic(1) (M1R) and muscarinic(4)(M4R) protein and mRNA as well as [(3)H]pirenzepine binding in Brodmann's areas (BA) 9 and 40 obtained postmortem from 20 schizophrenic and 20 age/sex-matched control subjects. There was a significant decrease in [(3)H]pirenzepine binding to BA 9 (mean +/- SEM: 151 +/- 15 vs 195 +/- 10 fmol mg(-1) ETE; P< 0.02), but not BA 40 (143 +/- 13 vs 166 +/- 11 fmol mg(-1) ETE), from subjects with schizophrenia. The level of M1R protein (0.11 +/- 0.007 vs 0.15 +/- 0.008 OD; P < 0.01), but not M4R protein, was decreased in BA9 from schizophrenic subjects with neither receptor protein being altered in BA 40. The level of M1R mRNA was decreased in BA 9 (30 +/- 7.0 vs 79 +/- 14 dpm x 10(3) mg(-1) ETE, P < 0.01) and BA 40 (28 +/- 5.9 vs 99 +/- 14, P < 0.01) with schizophrenia but M4R mRNA was only decreased in BA 40 (48 +/- 6.6 vs 89 +/- 9.9, P < 0.005). These data suggest that the M1R, at least in the dorsolateral prefrontal cortex, may have a role in the pathology of schizophrenia.

摘要

为了验证毒蕈碱受体参与精神分裂症病理过程这一假说，我们检测了20例精神分裂症患者及20例年龄和性别匹配的对照者死后获取的布罗德曼区（BA）9区和40区中毒蕈碱（1）（M1R）和毒蕈碱（4）（M4R）蛋白、mRNA以及[³H]哌仑西平结合情况。精神分裂症患者BA9区的[³H]哌仑西平结合显著降低（均值±标准误：151±15 vs 195±10 fmol mg⁻¹ ETE；P<0.02），但BA40区未降低（143±13 vs 166±11 fmol mg⁻¹ ETE）。精神分裂症患者BA9区的M1R蛋白水平降低（0.11±0.007 vs 0.15±0.008 OD；P<0.01），而M4R蛋白水平未降低，BA40区两种受体蛋白均未改变。精神分裂症患者BA9区和BA40区的M1R mRNA水平均降低（BA9区：30±7.0 vs 79±14 dpm×10³ mg⁻¹ ETE，P<0.01；BA40区：28±5.9 vs 99±14，P<0.01），但M4R mRNA仅在BA40区降低（48±6.6 vs 89±9.9，P<0.005）。这些数据表明，至少在背外侧前额叶皮质，M1R可能在精神分裂症的病理过程中起作用。