Neurosteroids affect induced cytotoxicity in SH-SY5Y cells differently
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
The major hypothesis behind the pathology of Alzheimer´s disease (AD) concerns a small peptide called the amyloid-β peptide (A-β). Deposition of A-β in the brain is regarded as one of the hallmarks of this devastating disease. Despite all scientific advances made in the field of AD pathology there is still no successful therapy to delay onset or slow progression of the disease. The major scientific breakthrough in the AD field is that pathological changes occur long before, 10 to 20 years, any symptoms are present. Neuroprotection against these early events of disease progression is therefore an interesting field of research. Neurosteroids, have been shown to exert proliferative and neuroprotective effects both in vivo and in vitro. In this study, the effects of the neurosteroids allopregnanolone (ALLO) and dehydroepiandrosterone sulfate (DHEA-S) on A-β associated cytotoxicity in the human neuroblastoma cell-line SH-SY5Y were investigated. A-βfailed to produce any significant toxicity in the SH-SY5Y cell line, instead staurosporine and hydrogen peroxide (H2O2) was used as surrogates for the A-β toxicity (staurosporine through mitochondrial apoptotic pathways and H2O2 through oxidative stress pathways). DHEA-S (0.1 μM) significantly inhibited H2O2 toxicity after 120 hours of incubation. This inhibition was not evident after 48 hours. Conversely DHEA-S (1 μM) inhibited staurosporine toxicity only after 48 h of incubation and not after 120 h. ALLO did not inhibit neither H2O2 nor staurosporine toxicity after any time of incubation. These results are in line with other studies of neurosteroid protection in vitro, where DHEA-S but not ALLO protected against H2O2 and staurosporine toxicity. Since the mechanisms behind A-β toxicity includes apoptotic cell death and oxidative stress it’s plausible that DHEA-S would protect against direct A-β toxicity, in a more toxicity-sensitive cell line, as well. The decrease in DHEA-S with age and in AD patients might render the cells more vulnerable to toxic insults.
Place, publisher, year, edition, pages
2013. , 22 p.
Neurosteroids, Amyloid beta peptide, DHEA-S, ALLO, SH-SY5Y, Cytotoxicity
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-203759OAI: oai:DiVA.org:uu-203759DiVA: diva2:637988
Subject / course
Master of Science Programme in Pharmacy
Svensson, Anne-Lie, Ph.D.
Nylander, Ingrid, Professor