Past Undergraduate Researchers
- Oliver Brady
- Elizabeth Flagge
- Rachel Leeson
- Patrick O'Malley
- Jennifer Ratliff
Roberts Research Group
The major research area in the Roberts lab focuses on the role of growth factors and sex steroids in mediating protection/recovery of the brain from damage due to oxidative stress, focusing on the nigro-striatal pathway and its degeneration in Parkinson’s disease. This whole system is characterized from a perspective of the changes that occur as the animal’s age progresses. Astrocytes, the largest cell population in the brain regulate neuronal homeostasis and have been implicated in affecting the viability and functioning of surrounding neurons under stressed conditions. In addition, much attention has been focused on estrogen interactions in non-neuronal cell types. Recent data from our lab suggests indirect actions of estrogen through ERa in neighboring glia to protect dopamine neurons against MPP+ toxicity in mouse mesencephalic or rat N27 dopaminergic cultures. These results prompted us to study estrogen signaling in astrocytes to evaluate the mechanism of estrogens indirect neuroprotective effects on DA neurons. E2 time course revealed a significant increase in Akt phosphorylation at 5-60 minutes. E2 also induced phosphorylation of the downstream transcription factor, CREB. These results were then analyzed in primary mesencephalic cultures in the presence of MPP+, which selectively damages DA neurons. Inhibition of Akt blocked E2 induced neuroprotection, implicating the involvement of the PI3 kinase pathway. Finally, E2 conditioned media collected from pure astrocyte cultures rescued glial deficient mesencephalic cultures from MPP+. This study demonstrates that estrogen signaling through astrocytes and the release of soluble factors, which includes BDNF, contributes significantly to the neuroprotection of DA neurons. This observation is supported by more recent studies performed by Trinity students utilizing culture insert wells separating the glia from the neurons with a permeable physical barrier and showing that the glia are still capable of protecting the neurons. Other students are characterizing the glial secreted proteins to understand exactly which proteins mediate this neuroprotection.
These observations are currently being expanded to the negative effects of androgens in this neuroprotective paradigm possibly explaining the bias of this disorder to males. It appears to be a direct mitochondrial effect on the dopaminergic neurons as opposed to mediation via glia. This would make an exciting summer project.
In a directly aging oriented study, we have cultured astroglia from young, middle-age and old mice and observed that the older astrocytes are less capable of protecting dopaminergic neurons from oxidative stress. We are currently characterizing this system using model dopaminerigic cultured cell lines.
Qualifications of successful applicants.
It is expected that the student will continue to work on this project during the subsequent year.
Sources of student funding
At this time, students applying to work in this lab must qualify for a research fellowship. No additional grant funding is available.
