The effect of coenzyme Q10 supplementation on mitochondrial chanes and neuroprotection in chronic celebral hypoperfusion-induced neurodegeneration in rats

Abstract

Neurodegeneration is highly associated with oxidative damage and mitochondrial dysfunction that are initiated by reduced cerebral blood flow in aging process. Alzheimer’s disease is the most common neurodegenerative disorder that has huge impact on societies and prevalence of this disease is rising rapidly without curative treatment. Permanent, bilateral common carotid arteries ligation (2 vessels occlusion-2VO) animal model has been established to study neurodegeneration, particularly Alzheimer’s disease which is correlated with chronic cerebral hypoperfusion. Coenzyme Q10 is a strong antioxidant and has been used in mitochondrial disorders and neurodegenerative disorders. The main objective of this study was to investigate the effect of the Coenzyme Q10 (CoQ10) on mitochondrial changes and neuroprotection in chronic cerebral hypoperfusion-induced neurodegeneration in 2VO model of rats. We studied the effect of CoQ10 on neuronal damage in the CA1 region of the dorsal hippocampus, oxidative stress level and mitochondrial morphological changes in pyramidal hippocampal cells. Rats were randomly divided into 4 groups, each group having 7 rats (n=7). The groups were as follows: sham control (C), untreated 2VO (2VO), vehicle treated 2VO (2VO+V) and Coenzyme Q10 treated group (2VO+CoQ10). After 8 weeks of treatment with CoQ10 and vehicle, right hippocampal tissue was dissected out and examined for viable neuronal cells in CA1 region under light microscope, and left hippocampal tissue was examined for measurement of TBARS level, ultrastructural and mitochondrial morphological changes under transmission electron microscope (TEM). 2VO+CoQ10 group revealed significantly higher number of viable cells in CA1 region of hippocampus than 2VO and 2VO+V groups (p<0.001). Likewise, TBARS concentration in hippocampus was significantly lower in 2VO+CoQ10 group than 2VO and 2VO+V groups (p<0.05). Furthermore, there was no significant difference of viable neuronal cells and TBARS concentration between sham control and 2VO+CoQ10 group. In TEM investigation, there was significant abnormal ultrastructural and mitochondrial morphological changes in 2VO group as compared with sham control group. However, 2VO+CoQ10 group showed significant improvement in ultrastructural and mitochondrial morphological changes while 2VO+V group did not show much mitochondrial morphological improvement. This present study revealed that chronic cerebral hypoperfusion in 2VO rats induced neuronal cell death, oxidative stress and mitochondrial dysfunction in the hippocampus of the brain. In addition, CoQ10 supplementation has therapeutic potential for the treatment of chronic cerebral hypoperfusion related neurodegenerative disorders such as Alzheimer’s disease by preventing oxidative damage and mitochondrial dysfunction.