Barr Alasdair M, Fish Kenneth N, Markou Athina, Honer William G
Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Eur J Neurosci. 2008 May;27(10):2568-74. doi: 10.1111/j.1460-9568.2008.06233.x.
Post mortem, reduced brain reelin is noted in schizophrenia. Accordingly, the reelin-haploinsufficient heterozygous reeler mouse (HRM) has been posited as a murine model of the illness. One study reported that HRM exhibit deficits in prepulse inhibition (PPI) of the acoustic startle reflex, a sensorimotor-gating behavior that is disrupted in schizophrenia, although this finding has not been reproduced. To extend the characterization of putative sensorimotor-gating deficits in HRM, these mice were subjected to a sophisticated series of PPI tests. Mice were tested in a cross-modal PPI protocol that combined an acoustic prepulse with a tactile startle stimulus and also in a protocol that included varying prepulse-pulse intervals and varying acoustic startle pulse intensities. Levels of acoustic startle habituation and cross-modal PPI were significantly lower in HRM, although unimodal PPI did not differ. The HRM also exhibited increased PPI compared to wildtypes at short interstimulus intervals between prepulse and pulse stimuli when the interval between the acoustic prepulse and pulse were varied, and were more reactive to higher intensity startle stimuli. Some of these deficits in sensorimotor gating parallel those of schizophrenia, a disease characterized by alterations in synaptic protein expression. Therefore, levels of presynaptic proteins were measured in multiple brain regions using ELISA in HRM. No significant alterations in presynaptic protein expression were found. Thus, HRM exhibit a complex pattern of changes in startle reactivity and sensorimotor gating, with both similarities to and differences from schizophrenia. However, it is unlikely that these behavioral differences may be accounted for by altered regional levels of presynaptic proteins.
尸检发现，精神分裂症患者大脑中的Reelin蛋白减少。因此，Reelin基因单倍体不足的杂合型Reeler小鼠（HRM）被认为是该疾病的小鼠模型。一项研究报告称，HRM在听觉惊吓反射的前脉冲抑制（PPI）方面存在缺陷，这是一种在精神分裂症中会受到破坏的感觉运动门控行为，不过这一发现尚未得到重复验证。为了进一步刻画HRM中假定的感觉运动门控缺陷，对这些小鼠进行了一系列复杂的PPI测试。小鼠在一种跨模态PPI实验方案中接受测试，该方案将听觉前脉冲与触觉惊吓刺激相结合，还在一种包含不同前脉冲 - 脉冲间隔和不同听觉惊吓脉冲强度的实验方案中接受测试。HRM的听觉惊吓习惯化水平和跨模态PPI显著较低，尽管单模态PPI没有差异。当改变听觉前脉冲和脉冲之间的间隔时，在短的前脉冲和脉冲刺激间隔下，HRM与野生型相比还表现出PPI增加，并且对更高强度的惊吓刺激反应更强。这些感觉运动门控方面的一些缺陷与精神分裂症的缺陷相似，精神分裂症是一种以突触蛋白表达改变为特征的疾病。因此，使用酶联免疫吸附测定法（ELISA）在HRM的多个脑区测量了突触前蛋白的水平。未发现突触前蛋白表达有显著改变。因此，HRM在惊吓反应性和感觉运动门控方面表现出复杂的变化模式，与精神分裂症既有相似之处也有不同之处。然而，这些行为差异不太可能由突触前蛋白的区域水平改变来解释。
