Mepham Jennifer R, MacFabe Derrick F, Boon Francis H, Foley Kelly A, Cain Donald P, Ossenkopp Klaus-Peter
Graduate Program in Neuroscience, Western University, London, Ontario, Canada; The Kilee Patchell-Evans Autism Research Group, Department of Psychology, Western University, London, Ontario, Canada.
Department of Psychology, Western University, London, Ontario, Canada; The Kilee Patchell-Evans Autism Research Group, Department of Psychology, Western University, London, Ontario, Canada.
Behav Brain Res. 2021 Apr 9;403:113140. doi: 10.1016/j.bbr.2021.113140. Epub 2021 Jan 27.
Propionic acid (PPA) is produced by enteric gut bacteria and is a dietary short chain fatty acid. Intracerebroventricular (ICV) infusions of PPA in rodents have been shown to produce behavioural changes, including adverse effects on cognition, similar to those seen in autism spectrum disorders (ASD). Previous research has shown that repeated ICV infusions of PPA result in impaired spatial learning in a Morris water maze (MWM) as evidenced by increased search latencies, fewer direct and circle swims, and more time spent in the periphery of the maze than control rats. In the current study rats were first given non-spatial pretraining (NSP) in the water maze in order to familiarize the animals with the general requirements of the non-spatial aspects of the task before spatial training was begun. Then the effects of ICV infusions of PPA on acquisition of spatial learning were examined. PPA treated rats failed to show the positive effects of the non-spatial pretraining procedure, relative to controls, as evidenced by increased search latencies, longer distances travelled, fewer direct and circle swims, and more time spent in the periphery of the maze than PBS controls. Thus, PPA treatment blocked the effects of the pretraining procedure, likely by impairing sensorimotor components or memory of the pretraining.
丙酸（PPA）由肠道细菌产生，是一种膳食短链脂肪酸。在啮齿动物中，脑室内（ICV）注射PPA已被证明会产生行为变化，包括对认知的不利影响，类似于自闭症谱系障碍（ASD）中的表现。先前的研究表明，重复脑室内注射PPA会导致在莫里斯水迷宫（MWM）中空间学习受损，表现为搜索潜伏期延长、直接和环形游泳次数减少，以及与对照大鼠相比，在迷宫周边花费的时间更多。在本研究中，大鼠首先在水迷宫中进行非空间预训练（NSP），以便在开始空间训练之前使动物熟悉任务非空间方面的一般要求。然后检查脑室内注射PPA对空间学习获得的影响。与对照组相比，PPA处理的大鼠未能表现出非空间预训练程序的积极效果，表现为搜索潜伏期延长、行进距离更长、直接和环形游泳次数减少，以及与PBS对照组相比，在迷宫周边花费的时间更多。因此，PPA处理可能通过损害感觉运动成分或预训练记忆来阻断预训练程序的效果。
