McFarland Ross, Wang Zi Teng, Jouroukhin Yan, Li Ye, Mychko Olga, Coppens Isabelle, Xiao Jianchun, Jones-Brando Lorraine, Yolken Robert H, Sibley L David, Pletnikov Mikhail V
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Behav Brain Res. 2018 Jul 16;347:193-200. doi: 10.1016/j.bbr.2018.03.023. Epub 2018 Mar 16.
Infection with the protozoan parasite, Toxoplasma gondii (T. gondii), has been associated with the increased risk for several psychiatric disorders. The exact mechanisms of a hypothesized contribution of T. gondii infection are poorly understood. The T. gondii genome contains two aromatic amino acid hydroxylase genes (AAH1 and AAH2) that encode proteins that can produce L-DOPA. One popular hypothesis posits that these encoded enzymes might influence dopamine (DA) production and hence DA synaptic transmission, leading to neurobehavioral abnormalities in the infected host. Prior studies have shown that deletion of these genes does not alter DA levels in the brain or exploratory activity in infected mice. However, possible effects of AAH gene deficiency on infection-induced brain and behavior alterations that are directly linked to DA synaptic transmission have not been evaluated. We found that chronic T. gondii infection of BALB/c mice leads to blunted response to amphetamine or cocaine and decreased expression of Dopamine Transporter (DAT) and Vesicular Monoamine Transporter 2 (VMAT2). Deletion of AAH2 had no effects on these changes in infected mice. Both wild type and Δaah2 strains produced comparable levels of neuroinflammation. Our findings demonstrate that AAH2 is not required for T. gondii infection-produced DA-dependent neurobehavioral abnormalities.
感染原生动物寄生虫刚地弓形虫（T. gondii）与多种精神疾病风险增加有关。关于刚地弓形虫感染假定作用的确切机制尚不清楚。刚地弓形虫基因组包含两个芳香族氨基酸羟化酶基因（AAH1和AAH2），它们编码的蛋白质可产生左旋多巴。一种流行的假说是，这些编码的酶可能会影响多巴胺（DA）的产生，进而影响DA突触传递，导致受感染宿主出现神经行为异常。先前的研究表明，删除这些基因不会改变感染小鼠大脑中的DA水平或探索活动。然而，尚未评估AAH基因缺陷对与DA突触传递直接相关的感染诱导的大脑和行为改变的可能影响。我们发现，BALB/c小鼠的慢性刚地弓形虫感染导致对苯丙胺或可卡因的反应迟钝，以及多巴胺转运体（DAT）和囊泡单胺转运体2（VMAT2）的表达降低。删除AAH2对感染小鼠的这些变化没有影响。野生型和Δaah2菌株产生的神经炎症水平相当。我们的研究结果表明，刚地弓形虫感染产生的DA依赖性神经行为异常不需要AAH2。
