Resolvin D1 ameliorates cognitive impairment following traumatic brain injury via protecting astrocytic mitochondria

AbstractCognitive impairment is one of the most common and devastating neuropsychiatric sequelae after traumatic brain injury (TBI), and hippocampal neuronal survival plays a causal role in this pathological process. Resolvin D1 (RvD1), an important endogenous specialized pro ‐resolving mediator, has recently been reported to exert a potent protective effect on mitochondria. This suggests that RvD1 may suppress neuroinflammation and protect astrocytic mitochondria at the same time to play further neuroprotective roles. C57BL/6 mice subjected to TBI using a controlled c ortical impact (CCI) device were used for in vivo experiments. Cultured primary mouse astrocytes and an N2a mouse neuroblastoma cell line were used for in vitro experiments. In TBI mice, RvD1 significantly ameliorated cognitive impairment, suppressed gliosis and alleviated neuronal loss in the hippo campus. To explore the mechanism underlying this activity, we verified that RvD1 can induce a higher level of mitophagy to remove damaged mitochondria and eliminate extra mitochondria‐derived reactive oxygen species (mitoROS) by activating ALX4/FPR2 receptors in astrocytes. In an in vitro model, w e further confirmed that RvD1 can protect mitochondrial morphology and membrane potential in astrocytes and thereby enhance the survival of neurons. Meanwhile, RvD1 was also shown to increase the expression of brain‐derived neurotrophic factor (BDNF) and glutamate aspartate transporter (GLAST) in the hippocampus foll...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research