Mycobacterium tuberculosis causes a leaky blood-brain barrier and neuroinflammation in the prefrontal cortex and cerebellum regions of infected mice offspring,International Journal of Developmental Neuroscience

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Mycobacterium tuberculosis causes a leaky blood-brain barrier and neuroinflammation in the prefrontal cortex and cerebellum regions of infected mice offspring
International Journal of Developmental Neuroscience ( IF 1.7 ) Pub Date : 2021-05-01 , DOI: 10.1002/jdn.10116
Wadzanai Manjeese ₁ , Nontobeko E Mvubu ₂ , Adrie J C Steyn _{2,

3,

4} , Thabisile Mpofana ₁

Affiliation

The maternal system's exposure to pathogens influences foetal brain development through the influx of maternal cytokines and activation of the foetal immune status to a persistent inflammatory state characterised by glia cell activation. Neuroinflammation influences the blood-brain barrier's (BBB) permeability allowing peripheral immune cell trafficking into the brain. Mycobacterium tuberculosis (Mtb) is a pathogen that causes Tuberculosis (TB), a global pandemic responsible for health and economic burdens. Although it is known that maternal infections increase the risk of Autism spectrum disorder (ASD), it is not known whether gestational Mtb infections also contribute to impaired foetal neurodevelopment. Here we infect pregnant Balb/c mice with Mtb H37Rv and Valproic acid (VPA) individually and in combination. Neuroinflammation was measured by assessing microglia and astrocyte population in the prefrontal cortex (PFC) and cerebellum (CER) of pups. Mtb infection increased the microglia population and caused morphological changes to a reactive phenotype in the PFC. Also, the astrocyte population was significantly increased in the PFC of Mtb pups. The BBB permeability was determined by measuring the Evans Blue (EB) dye concentration in the PFC and CER 1 hr post receiving intravenous EB-dye injection. We found that prenatal Mtb exposure significantly increased the BBB's permeability in the PFC and CER of pups versus saline. Overall, our data demonstrate that prenatal exposure to Mtb predisposes offspring to a higher risk of BBB damage while inducing persistent neuroinflammation, which could lead to impaired neuronal development and function. These findings implicate a potential role of gestational Mtb infections in the aetiology of ASD.

中文翻译：

结核分枝杆菌导致受感染小鼠后代的前额叶皮层和小脑区域出现血脑屏障渗漏和神经炎症

母体系统暴露于病原体，通过母体细胞因子的流入和胎儿免疫状态的激活影响胎儿大脑发育，从而形成以神经胶质细胞激活为特征的持续炎症状态。神经炎症会影响血脑屏障 (BBB) 的通透性，允许外周免疫细胞进入大脑。结核分枝杆菌( Mtb ) 是导致结核病 (TB) 的病原体，结核病是一种全球流行病，会造成健康和经济负担。尽管已知母体感染会增加自闭症谱系障碍 (ASD) 的风险，但尚不清楚妊娠Mtb感染是否也会导致胎儿神经发育受损。在这里，我们感染怀孕的 Balb/c 小鼠Mtb H37Rv 和丙戊酸 (VPA) 单独和组合。通过评估幼崽前额叶皮层 (PFC) 和小脑 (CER) 中的小胶质细胞和星形胶质细胞群来测量神经炎症。Mtb感染增加了小胶质细胞的数量，并导致 PFC 中反应性表型的形态变化。此外，Mtb幼崽的 PFC 中的星形胶质细胞数量显着增加。BBB 渗透性通过测量接受静脉注射 EB 染料后 1 小时 PFC 和 CER 中的伊文思蓝 (EB) 染料浓度来确定。我们发现，与生理盐水相比，产前Mtb暴露显着增加了幼崽 PFC 和 CER 中 BBB 的渗透性。总的来说，我们的数据表明，产前暴露于Mtb使后代更容易受到 BBB 损伤，同时诱发持续性神经炎症，这可能导致神经元发育和功能受损。这些发现暗示了妊娠Mtb感染在 ASD 病因学中的潜在作用。

更新日期：2021-05-01

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