Heterozygous reeler mice exhibit alterations in sensorimotor gating but not presynaptic proteins
Heterozygous reeler mice exhibit alterations in sensorimotor gating but not presynaptic proteins
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DOI：
10.1111/j.1460-9568.2008.06233.x
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发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Honer, William G.
中科院分区：
文献类型：
--
作者：
Barr, Alasdair M.;Fish, Kenneth N.;Honer, William G.
精神分裂症患者死后，大脑血管收缩减少。因此，reelin-haploinsufficient杂合子reeler小鼠（HRM）已被假定为该疾病的小鼠模型。一项研究报告称，HRM表现出听觉惊吓反射的前脉冲抑制（PPI）缺陷，这是一种在精神分裂症中被破坏的感觉运动门控行为，尽管这一发现尚未重现。为了扩展HRM中推定的感觉运动门控缺陷的表征，这些小鼠进行了一系列复杂的PPI测试。在将声学预脉冲与触觉惊吓刺激相结合的交叉模态PPI方案中以及在包括变化的预脉冲-脉冲间隔和变化的声学惊吓脉冲强度的方案中测试小鼠。HRM的声惊吓习惯和跨模态PPI水平显着较低，虽然单峰PPI没有差异。HRM也表现出增加PPI相比，野生型在短的刺激间隔之间的预脉冲和脉冲刺激时，声学预脉冲和脉冲之间的间隔是不同的，更高强度的惊吓刺激反应。感觉运动门控中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，在HRM中使用ELISA在多个脑区域中测量突触前蛋白的水平。突触前蛋白表达无明显改变，因此，HRM表现出一种复杂的惊吓反应性和感觉运动门控的变化模式，与精神分裂症既有相似之处，也有不同之处。然而，这是不可能的，这些行为差异可能是由突触前蛋白质的区域水平的改变。
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.