Illawarra Health and Medical Research Institute, Wollongong, New South Wales 2522 Australia.
School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522 Australia.
Sci Rep. 2016 Oct 10;6:34391. doi: 10.1038/srep34391.
Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically declining at adolescence and adulthood (-97-99%). The mGluR regulators, Homer 1b/c and Norbin, significantly increased with age in the PFC and hippocampus. Perinatal PCP treatment significantly increased juvenile dimeric mGluR5 levels in the PFC and hippocampus (37-50%) but decreased hippocampal mGluR1α (-50-56%). Perinatal PCP treatment also reduced mGluR1α dimer levels in the PFC at adulthood (-31%). These results suggest that Group 1 mGluRs have distinct dimeric and monomeric neurodevelopmental patterns, which may impact their pharmacological profiles at specific ages. Perinatal PCP treatment disrupted the early expression of Group 1 mGluRs which may underlie neurodevelopmental alterations observed in this model.
1 型代谢型谷氨酸受体（mGluR1/mGluR5）在神经发育中起着重要作用，并与精神疾病有关，如精神分裂症。mGluR1 和 mGluR5 表达为同源二聚体，这对于它们的功能和药理学非常重要。我们研究了在发育过程中（青少年/成年）以及精神分裂症的围产期苯环利定（PCP）模型中，前额叶皮层（PFC）和海马体中二聚体和单体 mGluR1α 和 mGluR5 的蛋白表达。在对照条件下，mGluR1α 二聚体表达在青少年期和成年期之间增加（209-328%），而单体水平保持一致。二聚体 mGluR5 一直稳定表达在所有时间点；单体 mGluR5 存在于青少年中，在青少年期和成年期急剧下降（-97-99%）。mGluR 调节剂 Homer 1b/c 和 Norbin 在 PFC 和海马体中随年龄的增长而显著增加。围产期 PCP 处理显著增加了 PFC 和海马体中青少年二聚体 mGluR5 的水平（37-50%），但降低了海马体 mGluR1α（-50-56%）。围产期 PCP 处理还降低了成年 PFC 中 mGluR1α 二聚体的水平（-31%）。这些结果表明，1 型 mGluR 具有不同的二聚体和单体神经发育模式，这可能会影响它们在特定年龄的药理学特征。围产期 PCP 处理破坏了 1 型 mGluR 的早期表达，这可能是该模型中观察到的神经发育改变的基础。
