Beneficial Effects of Blueberry Extracts on Adult Human Neural Progenitor Cells

Abstract

Abstract Objectives Aging-induced declines in neurogenesis and stem cell functions play a key role in the pathophysiology of age-associated neuronal disorders, and oxidative stress and inflammation are the major contributing factors. Blueberries, rich in polyphenols, have been shown to decrease oxidative stress, inflammation, and improve cognitive function in aged animals and humans. The current study investigated the effects of blueberry (BB) treatments on the viability, proliferation, fate choice, and expression of oxidative stress and inflammation markers of adult human neural progenitor cells (AHNPs), to establish mechanisms underlying the beneficial effects. Methods AHNPs derived from control and Parkinson's disease (PD) patients were pre-treated with various concentrations of freeze-dried BB extract for 7–10 days. Their viability and proliferation were examined using Trypan Blue exclusion and ethynyl-deoxyuridine (EdU) assay, respectively. Some treated cells were labeled with neuronal markers to examine their differentiation. Expression of oxidative stress and inflammation markers such as iNOS and Nox-2 was evaluated using western blot analysis. Whether BB could protect AHNPs from stress induced by dopamine (DA) was investigated by exposing cells to DA for 2–4 hours prior to evaluating their viability, proliferation, calcium buffering, and expression of oxidative stress and inflammation markers. Results Our data show that while BB treatment did not significantly affect the viability of control- and PD-AHNPs, BB extract significantly increased the proliferation rate of PD-AHNPs at higher concentrations. Additionally, BB treatment was able to revive the decrease in cell viability and proliferation following cellular stress induced by DA, indicating a potential neuroprotective effect. BB treatment was also able to protect against the harmful effects on Ca2+ buffering and reduce the increased expression levels of both iNOS and Nox-2 induced by DA exposure. Conclusions Blueberry extracts confer anti-oxidative, anti-inflammatory and neuroprotective effects on control and Parkinson's AHNPs, suggesting a role for dietary nutrients in helping to slow progression of neural dysfunction and neurodegenerative disease during aging. Funding Sources Supported by USDA/ARS intramural grant, and the Robert and Margaret Patricelli Family Foundation.