Shultz Sandy R, Aziz Noor A B, Yang Li, Sun Mujun, MacFabe Derrick F, O'Brien Terence J
Melbourne Brain Centre, Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
Melbourne Brain Centre, Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
Behav Brain Res. 2015 Feb 1;278:542-8. doi: 10.1016/j.bbr.2014.10.050. Epub 2014 Nov 6.
Autism is a complex neurodevelopmental disorder that is characterized by social abnormalities. Genetic, dietary and gut-related factors are implicated in autism, however the causal properties of these factors and how they may interact are unclear. Propionic acid (PPA) is a product of gut microbiota and a food preservative. PPA has been linked to autism, and PPA administration to rats is an animal model of the condition. Seizure-prone (FAST) and seizure-resistant (SLOW) rats were initially developed to investigate differential vulnerability to developing epilepsy. However, FAST rats also display autistic-like features, and have been proposed as a genetic model of autism. Here we examined the effects of PPA on social behavior in FAST and SLOW rats. A single intracerebroventricular injection of PPA, or phosphate-buffered saline (PBS), was administered to young-adult male FAST and SLOW rats. Immediately after treatment, rats were placed in same-treatment and same-strain pairs, and underwent social behavior testing. PPA induced social abnormalities in both FAST and SLOW rat strains. While there was no evidence of social impairment in FAST rats that were not treated with PPA, these rats were hyperactive relative to SLOW rats. Post-mortem immunofluorescence analysis of brain tissue indicated that PPA treatment resulted in increased astrogliosis in the corpus callosum and cortex compared to PBS treatment. FAST rats had increased astrogliosis in the cortex compared to SLOW rats. Together these findings support the use of PPA as a rat model of autism, but indicate there are no interactive effects between the PPA and FAST models.
自闭症是一种复杂的神经发育障碍，其特征为社交异常。遗传、饮食和肠道相关因素与自闭症有关，然而这些因素的因果性质以及它们之间可能如何相互作用尚不清楚。丙酸（PPA）是肠道微生物群的产物，也是一种食品防腐剂。PPA与自闭症有关，给大鼠施用PPA是该病症的一种动物模型。易癫痫发作（FAST）大鼠和抗癫痫发作（SLOW）大鼠最初是为研究癫痫易感性差异而培育的。然而，FAST大鼠也表现出自闭症样特征，并被提议作为自闭症的遗传模型。在此，我们研究了PPA对FAST和SLOW大鼠社交行为的影响。对成年雄性FAST和SLOW大鼠进行单次脑室内注射PPA或磷酸盐缓冲盐水（PBS）。治疗后立即将大鼠按相同处理和相同品系配对，并进行社交行为测试。PPA在FAST和SLOW大鼠品系中均诱发了社交异常。虽然未用PPA处理的FAST大鼠没有社交障碍的证据，但这些大鼠相对于SLOW大鼠活动过度。脑组织的死后免疫荧光分析表明，与PBS处理相比，PPA处理导致胼胝体和皮质中的星形胶质细胞增生增加。与SLOW大鼠相比，FAST大鼠皮质中的星形胶质细胞增生增加。这些发现共同支持将PPA用作自闭症大鼠模型，但表明PPA模型和FAST模型之间没有交互作用。
