Darwish Batoul, Chamaa Farah, Al-Chaer Elie D, Saadé Nayef E, Abou-Kheir Wassim
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Front Neurosci. 2019 Jul 3;13:687. doi: 10.3389/fnins.2019.00687. eCollection 2019.
Brain inflammation can result in functional disorders observed in several neurodegenerative diseases and that can be also associated with reduced neurogenesis. In this study, we investigate the effect of mild inflammation, induced by unilateral injection of Endotoxin (ET) in the substantia nigra (SN)/Ventral Tegmental Area, on the proliferation and survival of stem/progenitor cells in the dentate gyrus (DG) of the hippocampus. Adult female rats received unilateral injection of ET (2 μg/2 μl saline) or sterile saline (2 μl) in the right SN followed by 5'-Bromo-2'-deoxyuridine (BrdU) injections (66 mg/kg/injection). Intranigral ET injection induced bilateral decrease in the number of newly born BrdU positive cells in the DG. This effect was paralleled by a significant decrease in the exploratory behavior of rats, as assessed by the Y-maze novel arm exploration task. ET also induced a transient decrease in the number of tyrosine hydroxylase-positive cells in the injected SN, impaired motor behavior, and caused microglial activation in the SN. This study provides an experimental simulation of the remote effects of moderate and reversible neuroinflammation resulting in impaired communication between midbrain dopaminergic neurons and the hippocampus.
脑炎症可导致在几种神经退行性疾病中观察到的功能障碍，并且还可能与神经发生减少有关。在本研究中，我们研究了通过向黑质（SN）/腹侧被盖区单侧注射内毒素（ET）诱导的轻度炎症对海马齿状回（DG）中干细胞/祖细胞增殖和存活的影响。成年雌性大鼠在右侧SN接受单侧注射ET（2μg/2μl生理盐水）或无菌生理盐水（2μl），随后注射5'-溴-2'-脱氧尿苷（BrdU）（66mg/kg/注射）。黑质内注射ET导致DG中新生BrdU阳性细胞数量双侧减少。通过Y迷宫新臂探索任务评估，这种效应与大鼠探索行为的显著减少同时出现。ET还导致注射侧SN中酪氨酸羟化酶阳性细胞数量短暂减少，损害运动行为，并引起SN中的小胶质细胞活化。本研究提供了中度和可逆性神经炎症远程效应的实验模拟，导致中脑多巴胺能神经元与海马之间的通讯受损。
