Dysregulation of kisspeptin and neurogenesis at adolescence link inborn immune deficits to the late onset of abnormal sensorimotor gating in congenital psychological disorders
Dysregulation of kisspeptin and neurogenesis at adolescence link inborn immune deficits to the late onset of abnormal sensorimotor gating in congenital psychological disorders
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DOI：
10.1038/mp.2009.66
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发表时间：
2010-04-01
影响因子：
11
通讯作者：
Schwartz, M.
中科院分区：
文献类型：
--
作者：
Cardon, M.;Ron-Harel, N.;Schwartz, M.
包括精神分裂症在内的神经心理综合征通常直到青春期末或成年早期才会显现。将大脑维护的作用归因于免疫系统的研究使我们提出，青春期大脑功能的免疫依赖性调节功能障碍是此类疾病/综合征迟发的基础。其中一项功能是感觉运动门控，即分离连续的感觉和认知信息流，并通过沉默背景（通过前脉冲抑制测量；PPI）选择性地将注意力分配到重要事件的能力。这种活性在精神分裂症以及其他几种神经心理疾病中受到损害。使用产前免疫激活模型（母体聚核糖肌苷-聚核糖胞苷酸（聚 I:C）注射），通常用作精神分裂症模型，并且异常 PPI 延迟出现，我们在成年后代中证明了一种形式的免疫缺陷。在先天性免疫缺陷小鼠（严重联合免疫缺陷，SCID）中也发现了类似的延迟出现的异常 PPI，并且可以通过免疫重建来逆转。这种功能缺陷与成年期表现出的海马神经发生和编码 Kisspeptin (Kiss1) 的基因表达受损相关。此外，外源性给予 Kisspeptin 衍生肽可部分逆转 SCID 小鼠的门控缺陷。我们的研究结果表明，某种形式的先天性免疫缺陷可能是决定仅在成年早期发病的发育性神经心理障碍表现的关键因素。分子精神病学 (2010) 15, 415-425; doi：10.1038/mp.2009.66； 2009 年 7 月 28 日在线发布
Neuropsychological syndromes including schizophrenia often do not manifest until late adolescence or early adulthood. Studies attributing a role in brain maintenance to the immune system led us to propose that malfunction of immune-dependent regulation of brain functions at adolescence underlies the late onset of such diseases/syndromes. One such function is sensorimotor gating, the ability to segregate a continuous stream of sensory and cognitive information, and to selectively allocate attention to a significant event by silencing the background (measured by prepulse inhibition; PPI). This activity is impaired in schizophrenia, as well as in several other neuropsychological diseases. Using a model of prenatal immune activation (maternal polyriboinosinic-polyribocytidylic acid (poly I: C) injection), often used as a model for schizophrenia, and in which abnormal PPI has a delayed appearance, we demonstrated a form of immune deficit in the adult offspring. Similar abnormal PPI with a delayed appearance was found in congenitally immune-deficient mice (severe combined immune deficient, SCID), and could be reversed by immune reconstitution. This functional deficit correlated with impairment of both hippocampal neurogenesis and expression of the gene encoding kisspeptin (Kiss1) that manifested at adulthood. Moreover, exogenous administration of a kisspeptin-derived peptide partially reversed the gating deficits in the SCID mice. Our results suggest that a form of congenital immune deficiency may be a key factor that determines manifestation of developmental neuropsychological disorders with onset only at early adulthood. Molecular Psychiatry (2010) 15, 415-425; doi: 10.1038/mp.2009.66; published online 28 July 2009