Reynolds Gavin P, Neill Joanna C
Sheffield Hallam University, Biomolecular Sciences Research Centre, Sheffield, UK.
Manchester Pharmacy School, University of Manchester, Manchester, UK
J Psychopharmacol. 2016 Nov;30(11):1141-1144. doi: 10.1177/0269881116667668. Epub 2016 Sep 13.
Here, Reynolds and Neill describe the studies that preceded and followed publication of this paper, which reported a deficit in parvalbumin (PV), a calcium-binding protein found in GABA interneurons known to be reduced in schizophrenia patients, in conjunction with a deficit in reversal learning in an animal model for schizophrenia. This publication resulted from common research interests: Reynolds in the neurotransmitter pathology of schizophrenia, and Neill in developing animal models for schizophrenia symptomatology. The animal model, using a sub-chronic dosing regimen (sc) with the non-competitive NMDA receptor antagonist PCP (phencyclidine), evolved from previous work in rats (for PCP) and primates (for cognition). The hypothesis of a PV deficit came from emerging evidence for a GABAergic dysfunction in schizophrenia, in particular a deficit in PV-containing GABA interneurons. Since this original publication, a PV deficit has been identified in other animal models for schizophrenia, and the PV field has expanded considerably. This includes mechanistic work attempting to identify the link between oxidative stress and GABAergic dysfunction using this scPCP model, and assessment of the potential of the PV neuron as a target for new antipsychotic drugs. The latter has included development of a molecule targeting KV3.1 channels located on PV-containing GABA interneurons which can restore both PV expression and cognitive deficits in the scPCP model.
在此，雷诺兹和尼尔描述了在本文发表之前及之后开展的研究。本文报道了小白蛋白（PV）的缺陷，PV是一种在GABA中间神经元中发现的钙结合蛋白，已知在精神分裂症患者中含量降低，同时还报道了精神分裂症动物模型中逆向学习的缺陷。这一出版物源于共同的研究兴趣：雷诺兹专注于精神分裂症的神经递质病理学，而尼尔致力于开发精神分裂症症状学的动物模型。该动物模型采用非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环利定（PCP）的亚慢性给药方案（sc），它是从先前在大鼠（针对PCP）和灵长类动物（针对认知）方面的研究发展而来的。PV缺陷的假说源于精神分裂症中GABA能功能障碍的新证据，特别是含PV的GABA中间神经元的缺陷。自这一最初的出版物发表以来，在其他精神分裂症动物模型中也发现了PV缺陷，并且PV领域有了相当大的扩展。这包括利用这种scPCP模型试图确定氧化应激与GABA能功能障碍之间联系的机制研究，以及评估PV神经元作为新型抗精神病药物靶点的潜力。后者包括开发一种靶向位于含PV的GABA中间神经元上的KV3.1通道的分子，该分子可恢复scPCP模型中的PV表达和认知缺陷。
