Protective capabilities of allopregnanolone against induced toxicity in SH-SY5Y cells relative to Alzheimer´s disease.

Sammanfattning: When the brain is exposed to a traumatic injury, the brain produces high amounts of neurosteroids like allopregnanolone and progesterone which show protective and neurogenic capacities. Alzheimer’s disease patients also have lower amounts of these neurosteroids in brain tissue. Neurosteroids act on GABAA receptors and cholesterol receptors which is interesting since both the cholesterol transporter ApoE and excitotoxicity seems to be issues plaguing the patients. To study if there is a relationship between Alzheimer’s disease and neurosteroids, there are ongoing phase one studies but neurobiological studies are equally important in order to understand the mechanism. In this work protective capabilities of allopregnanolone on induced toxicity was investigated in human neuroblastoma SH-SY5Y cells. Protection and induced toxicity were assessed by studying cell viability with MTT assay. Toxins used were the oxidative stress inducing agent t-BHP, excitotoxic glutamate and amyloid β25-35. Previous studies have found allopregnanolone to induce neurogenesis, decrease ROS levels, inhibit apoptosis and to have immunoregulatory capabilities. The present study did see an increase in cell viability when treated to 1x10-8 M allopregnanolone but this effect was not observed when the concentration was increased further to 1x10-7 M and 1x10-6 M. When the SH-SY5Y cells were treated with toxins after pretreatment of allopregnanolone, additional decrease was seen when compared to cells only treated with toxins. The present study discovered the influence of components like cell density and cell generation which is of value for researchers planning future neurobiological studies. These neurobiological studies give insight of the correct mechanisms in the brain, opening up opportunities for new efficient drugs to be developed.