Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism.
Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism.
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DOI：
10.1371/journal.pone.0048975
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kuhn DM
中科院分区：
文献类型：
--
作者：
Kane MJ;Angoa-Peréz M;Briggs DI;Sykes CE;Francescutti DM;Rosenberg DR;Kuhn DM
自闭症是一种复杂的神经发育障碍，其特征是相互社会互动受损，沟通障碍和重复行为。大量的基因与自闭症有关，其中许多基因编码的蛋白质参与突触回路的发育和功能。然而，这些突变基因可能单独或共同参与导致自闭症的方式尚不清楚。已知对大脑发育和网络形成产生极其广泛影响且与自闭症有关的一个因素是神经递质血清素。不幸的是，人们对5-羟色胺神经元功能的改变如何导致自闭症知之甚少。为了验证血清素功能障碍可能导致自闭症核心症状的假设，我们分析了缺乏脑血清素（通过色氨酸羟化酶2（TPH 2）基因的无效突变）的小鼠与这种疾病相关的行为。缺乏大脑血清素（TPH 2 −/−）的小鼠在许多有效的社会互动和沟通测试中表现出严重的缺陷。这些小鼠还表现出高度重复和强迫行为。新生的TPH 2 −/−突变小鼠在关键发育里程碑的表达上表现出延迟，并且它们对母体气味的偏好减弱，而不是对无关雌性气味的偏好，这是更严重的社会化缺陷的前兆，这些缺陷在断奶后出现并持续到成年。总之，这些结果表明，低血清素条件可以导致行为特征，是自闭症的高度特征。我们的研究结果应该刺激新的研究，重点是确定在关键的神经发育时期，大脑低胆固醇血症如何改变已知在自闭症中错误连接的突触回路的成熟，以及如何预防这种缺陷可能会预防这种疾病。
Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. A very large number of genes have been linked to autism, many of which encode proteins involved in the development and function of synaptic circuitry. However, the manner in which these mutated genes might participate, either individually or together, to cause autism is not understood. One factor known to exert extremely broad influence on brain development and network formation, and which has been linked to autism, is the neurotransmitter serotonin. Unfortunately, very little is known about how alterations in serotonin neuronal function might contribute to autism. To test the hypothesis that serotonin dysfunction can contribute to the core symptoms of autism, we analyzed mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder. Mice lacking brain serotonin (TPH2−/−) showed substantial deficits in numerous validated tests of social interaction and communication. These mice also display highly repetitive and compulsive behaviors. Newborn TPH2−/− mutant mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood. Taken together, these results indicate that a hypo-serotonin condition can lead to behavioral traits that are highly characteristic of autism. Our findings should stimulate new studies that focus on determining how brain hyposerotonemia during critical neurodevelopmental periods can alter the maturation of synaptic circuits known to be mis-wired in autism and how prevention of such deficits might prevent this disorder.
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影响因子：
2.7
作者：
Boylan, Carolyn B.;Blue, Mary E.;Hohmann, Christine F.
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0810793106
发表时间：
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