Ragu-Varman Durairaj, Macedo-Mendoza Mayra, Labrada-Moncada Francisco Emmanuel, Reyes-Ortega Pamela, Morales Teresa, Martínez-Torres Ataúlfo, Reyes-Haro Daniel
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla, Querétaro, CP76230, Mexico.
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla, Querétaro, CP76230, Mexico.
Behav Brain Res. 2019 May 2;363:118-125. doi: 10.1016/j.bbr.2019.01.042. Epub 2019 Jan 25.
Anorexia by osmotic dehydration is an adaptive response to hypernatremia and hyperosmolaemia induced by ingestion of a hypertonic solution. Dehydration-induced anorexia (DIA) reproduces weight loss and avoidance of food, despite its availability. By using this model, we previously showed increased reactive astrocyte density in the rat dorsal hippocampus, suggesting a pro-inflammatory environment where microglia may play an important role. However, whether such anorexic condition increases a pro-inflammatory response is unknown. The aim of this study was to test if DIA increases microglial density in the dorsal hippocampus, as well as the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β) in the hippocampus of young female rats. Our results showed that DIA significantly increased microglial density in CA2-CA3 and dentate gyrus (DG) but not in CA1. However, forced food restriction (FFR) only increased microglial density in the DG. Accordingly, the activated/resting microglia ratio was significantly increased in CA2-CA3 and DG, in DIA and FFR groups. Finally, western blot analysis showed increased expression of IBA1, TNF-α, IL-6 and IL-1β in the hippocampus of both experimental groups. We conclude that anorexia triggers increased reactive microglial density and expression of TNF-α, IL-6 and IL-1β; this environment may result in hippocampal neuroinflammation.
渗透性脱水引起的厌食是对摄入高渗溶液诱导的高钠血症和高渗血症的一种适应性反应。脱水诱导的厌食（DIA）会导致体重减轻和对食物的回避，即便食物可得。通过使用该模型，我们之前发现大鼠背侧海马中反应性星形胶质细胞密度增加，提示存在一种小胶质细胞可能发挥重要作用的促炎环境。然而，这种厌食状态是否会增加促炎反应尚不清楚。本研究的目的是测试DIA是否会增加年轻雌性大鼠海马背侧的小胶质细胞密度，以及海马中促炎细胞因子肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和白细胞介素1β（IL-1β）的表达。我们的结果显示，DIA显著增加了CA2-CA3和齿状回（DG）中的小胶质细胞密度，但CA1区未增加。然而，强制食物限制（FFR）仅增加了DG中的小胶质细胞密度。相应地，在DIA和FFR组中，CA2-CA3和DG中活化/静止小胶质细胞的比例显著增加。最后，蛋白质印迹分析显示两个实验组海马中IBA1、TNF-α、IL-6和IL-1β的表达均增加。我们得出结论，厌食会引发反应性小胶质细胞密度增加以及TNF-α、IL-6和IL-1β的表达增加；这种环境可能导致海马神经炎症。
