Hollins Sharon L, Brock Luke, Barreto Rafael, Harms Lauren, Dunn Ariel, Garcia-Sobrinho Pedro, Bruce Jessica, Dickson Phillip W, Walker Marjorie M, Keely Simon, Hodgson Deborah M
Laboratory of Neuroimmunology, School of Psychology, University of Newcastle, Callaghan, New South Wales, Australia,
Priority Research Centre for Brain and Mental Health Research, University of Newcastle, Callaghan, New South Wales, Australia,
Neuroimmunomodulation. 2018;25(3):163-175. doi: 10.1159/000493320. Epub 2018 Nov 9.
Gastrointestinal (GI) inflammation and GI integrity deficits are common comorbidities of neuropsychiatric disorders. Ongoing research suggests that these aberrations may be contributing to heightened immune signals that have the potential to disrupt neuronal homeostasis and exacerbate behavioural deficits. The current study aimed to determine whether the well-characterized animal model of neuropsychopathology, the maternal immune activation (MIA) model, produced GI inflammation and integrity disruptions in association with anxiety-like behaviour.
Pregnant Wistar rats were exposed to the viral mimetic polyriboinosinic:polyribocytidilic acid (polyI:C) on gestational days (GD) 10 and 19. Evidence of ANS activation, GI inflammation, and GI barrier integrity was assessed in both neonatal (postnatal day, P7) and adult (P84) offspring. Anxiety-like behaviour was assessed at P100.
Neonatal MIA offspring exhibited an altered intestinal inflammatory profile and evidence of an increase in lymphoid aggregates. MIA neonates also displayed disruptions to GI barrier tight junction protein mRNA. In addition, adult MIA offspring exhibited an increase in anxiety-like behaviours.
These results indicate that the MIA rat model, which is well documented to produce behavioural, neurochemical, and neuroanatomical abnormalities, also produces GI inflammation and integrity disruptions. We suggest that this model may be a useful tool to elucidate biological pathways associated with neuropsychiatric disorders.
胃肠道（GI）炎症和胃肠道完整性缺陷是神经精神疾病常见的合并症。正在进行的研究表明，这些异常可能导致免疫信号增强，进而破坏神经元内环境稳定并加剧行为缺陷。本研究旨在确定神经精神病理学中特征明确的动物模型——母体免疫激活（MIA）模型是否会产生胃肠道炎症和完整性破坏，并伴有焦虑样行为。
在妊娠第10天和第19天，将怀孕的Wistar大鼠暴露于病毒模拟物聚肌苷酸：聚胞苷酸（polyI:C）。在新生（出生后第7天，P7）和成年（P84）后代中评估自主神经激活、胃肠道炎症和胃肠道屏障完整性的证据。在P100评估焦虑样行为。
新生MIA后代表现出肠道炎症特征改变以及淋巴聚集增加的证据。MIA新生大鼠还表现出胃肠道屏障紧密连接蛋白mRNA的破坏。此外，成年MIA后代表现出焦虑样行为增加。
这些结果表明，MIA大鼠模型，其已被充分证明会产生行为、神经化学和神经解剖学异常，也会产生胃肠道炎症和完整性破坏。我们认为该模型可能是阐明与神经精神疾病相关生物学途径的有用工具。
