Crosslink between mutations in mitochondrial genes and brain disorders:implications for mitochondrial-targeted therapeutic interventions

At the present,association of mitochondrial dysfunction and progression of neurological disorders has gained significant attention.Defects in mitochondrial network dynamics,point mutations,deletions,and interaction of pathogenomic proteins with mitochondria are some of the possible underlying mechanisms involved in these neurological disorders.Mitochondrial genetics,defects in mitochondrial oxidative phosphorylation machinery,and reactive oxygen species production might share common crosstalk in the progression of these neurological disorders.It is of significant interests to explore and develop therapeutic strategies aimed at correcting mitochondrial abnormalities.This review provided insights on mitochondrial dysfunction/mutations involved in the progression of Alzheimer’s disease,Huntington’s disease,and epilepsy with a special focus on Parkinson’s disease pathology.Along with the deleterious effects of mitochondrial mutations in aforesaid neurological disorders,this paper unraveled the available therapeutic strategy,specifically aiming to improve mitochondrial dysfunction,drugs targeting mitochondrial proteins,gene therapies aimed at correcting mutant mtDNA,peptide-based approaches,and lipophilic cations.

Effects of vascular endothelial growth factor supplementation and alginate embedding on human oocyte maturation in vitro

Objective:To evaluate whether the use of vascular endothelial growth factor(VEGF)with alginate increases oocyte maturation following in vitro maturation.Methods:This experimental study was performed on 150 immature oocytes(germinal vesicle oocytes)from females who were candidates for assisted reproductive technology.The germinal vesicle oocytes were randomly placed in the control,alginate,and VEGF plus alginate groups.The basic culture medium for oocytes culture(tissue culture medium 199,follicle-stimulating hormone 0.075 IU/mL,and fetal bovine serum 10%)was used in the control,alginate,and VEGF plus alginate groups.For the treatment groups(alginate,and VEGF plus alginate groups),alginate(8%)and VEGF(5 ng/mL)were added to the basic culture medium.After culture,immature oocytes were considered as oocytes unchanged in the nucleus whereas oocytes with a polar body were considered as mature oocytes(metaphaseⅡstage).The mature oocytes in each group were fertilized by intracytoplasmic sperm injection and formed embryos were evaluated by reverse microscope.Results:The oocyte maturation rate(metaphaseⅡ)significantly(P<0.05)increased in the alginate plus VEGF group as compared with the alginate alone and control groups during in vitro maturation.On day 2,the cleavage rates were significantly different in the matured oocytes between the treatment groups and the control group.The percentage of the two-cell stage,four-cell stage and eight-cell embryos was significantly higher in the treatment groups compared with the control group(P<0.05).Conclusions:Supplementation of VEGF with alginate can improve oocyte maturation in culture media.VEGF with alginate may promote the quality of nuclear and cytoplasmic maturation of human oocytes in vitro.