Pre- and neonatal exposure to lipopolysaccharide or the enteric metabolite, propionic acid, alters development and behavior in adolescent rats in a sexually dimorphic manner.
Pre- and neonatal exposure to lipopolysaccharide or the enteric metabolite, propionic acid, alters development and behavior in adolescent rats in a sexually dimorphic manner.
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DOI：
10.1371/journal.pone.0087072
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Macfabe DF
中科院分区：
文献类型：
--
作者：
Foley KA;Ossenkopp KP;Kavaliers M;Macfabe DF
肠道微生物组和/或免疫系统功能组成的改变可能在自闭症谱系障碍（ASD）的发展中起作用。目前的研究检查了产前和生命早期管理的脂多糖（LPS），细菌模拟物，和短链脂肪酸，丙酸（PPA），肠细菌的代谢发酵产物，对发育里程碑的影响，自发活动，和焦虑样行为的青少年男性和女性后代。妊娠Long-Evans大鼠在妊娠第12 -16天每天皮下注射一次PPA（500 mg/kg），在妊娠第15 -16天皮下注射LPS（50 µg/kg），或在妊娠第12 -16天或妊娠第15 -16天皮下注射溶剂对照。雄性和雌性后代从出生后第10-18天（P）开始，每隔一天注射PPA（500 mg/kg）或溶剂，每天两次。在生命早期监测身体里程碑和反射，产前PPA和LPS诱导睁眼延迟。在高架十字迷宫和开放视野中评估青春期（P40-42）的运动活动和焦虑。产前和产后的治疗改变了行为的性别特异性的方式。产前PPA减少了雄性和雌性大鼠在旷场中心的时间，而产前和产后PPA增加了雌性大鼠在旷场中心的焦虑行为。产前LPS对这些行为没有显著影响。双重打击假说的证据被视为女性接受双重打击的PPA（产前和产后）显示增加重复行为在开放领域。这些结果为以下假设提供了证据：肠道细菌代谢的副产物（如PPA）可能导致ASD，改变青春期大鼠的发育和行为，类似于在ASD和其他神经发育障碍中观察到的情况。
Alterations in the composition of the gut microbiome and/or immune system function may have a role in the development of autism spectrum disorders (ASD). The current study examined the effects of prenatal and early life administration of lipopolysaccharide (LPS), a bacterial mimetic, and the short chain fatty acid, propionic acid (PPA), a metabolic fermentation product of enteric bacteria, on developmental milestones, locomotor activity, and anxiety-like behavior in adolescent male and female offspring. Pregnant Long-Evans rats were subcutaneously injected once a day with PPA (500 mg/kg) on gestation days G12–16, LPS (50 µg/kg) on G15–16, or vehicle control on G12–16 or G15–16. Male and female offspring were injected with PPA (500 mg/kg) or vehicle twice a day, every second day from postnatal days (P) 10–18. Physical milestones and reflexes were monitored in early life with prenatal PPA and LPS inducing delays in eye opening. Locomotor activity and anxiety were assessed in adolescence (P40–42) in the elevated plus maze (EPM) and open-field. Prenatal and postnatal treatments altered behavior in a sex-specific manner. Prenatal PPA decreased time spent in the centre of the open-field in males and females while prenatal and postnatal PPA increased anxiety behavior on the EPM in female rats. Prenatal LPS did not significantly influence those behaviors. Evidence for the double hit hypothesis was seen as females receiving a double hit of PPA (prenatal and postnatal) displayed increased repetitive behavior in the open-field. These results provide evidence for the hypothesis that by-products of enteric bacteria metabolism such as PPA may contribute to ASD, altering development and behavior in adolescent rats similar to that observed in ASD and other neurodevelopmental disorders.
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影响因子：
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作者：
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通讯作者：
Boksa, P
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