Janusonis Skirmantas
Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA.
Theor Biol Med Model. 2005 Jul 19;2:27. doi: 10.1186/1742-4682-2-27.
A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin) in blood platelets (platelet hyperserotonemia). The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor.
The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals.
At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene) based on currently available clinical and experimental studies.
已有报道称自闭症患者大脑存在广泛的异常情况,但这些异常可能是早期潜在发育改变的结果,到自闭症被诊断时,这种改变可能已不明显。自闭症个体最一致的生物学发现是其血小板中5-羟色胺(5-HT,血清素)水平在统计学上升高(血小板高血清素血症)。自闭症大脑的早期发育改变和自闭症血小板高血清素血症可能分别由大脑内和大脑外表达的相同生物学因素引起。与大脑不同,血小板寿命较短且在整个生命周期中持续产生,这表明该因素可能在大脑形成多年后仍在大脑外发挥作用。正常组和自闭症组血小板5-HT水平的统计分布具有特征性,可能包含有关这个尚未确定因素性质的信息。
通过一种新颖的定量方法研究了该因素的特性,该方法应用于已发表的正常组和自闭症组血小板5-HT水平的分布。结果表明,已发表的数据与以下假设一致:在自闭症中干扰大脑发育的因素也可能调节肠道肠嗜铬细胞中5-HT的释放。数值分析表明,该因素在自闭症个体中可能无功能。
至少一些生物学因素,其异常功能导致自闭症大脑的发育,可能在出生多年后调节肠道中5-HT的释放。如果当前模型正确,将使未来的研究能够集中在有限数量的基因候选物上,其中一些基于目前可用的临床和实验研究尚未被怀疑与自闭症有关(如5-HT4受体基因)。