A Possible Rejuvenation of Neurons Using Human Umbilical Cord Blood Through the Akt Pathway

Vijay Mehta

Date of Award

2011

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Beulig, Alfred

Keywords

Human Umbilical Cord Blood, Akt, Neurons

Area of Concentration

Neurobiology

Abstract

In the last 20 years the use of Human Umbilical Cord Blood Cells (CB), specifically the mononuclear cellular fraction of HUCB (MNC), has become an important therapy in multiple diseases, such as leukemia, and tissue degeneration. In the last 10 years the use of CB has been expanded to include neurodegenerative diseases and traumatic brain injuries. Its use in in vivo studies of stroke and traumatic brain injury has resulted in more than 80% recovery of brain cells in damaged areas. Studies have elucidated that the peripheral response, the cells outside the brain, is responsible for much of the neuronal death in strokes. The addition of CB at specific time points therefore allows it to intercede with the peripheral response, and promote the production of anti-inflammatory cytokines such as IL-10. This experiment examined the potential cell survival pathways that mediate CB's therapeutic effects on neurons. The two main pathways are the phosphoinositide 3-kinase/Akt (PI3K/Akt), and mitogen activated protein kinase/ extracellular signal-regulated kinase (MAPK/ERK). Neurons were collected and used in oxygen and glucose deprived conditions (OGD) which simulate the ambient conditions in ischemic stroke. Control groups were exposed to normal levels of oxygen and glucose. Each condition was treated with either Akt or ERK inhibitor as well as co-culture with CB. Results demonstrated that both pathways are significant in protecting neurons during exposure to OGD conditions, but the Akt effect was more significant in normoxic conditions. In OGD conditions cell viability for neurons with CB was at 79�7.26. This decreased significantly (p<0.01) to 46.7�2.02 when treated with CB and Akt inhibitor. The same conditions, but with MAPK inhibitor showed a significant (p<0.05) decrease in cell viability from 80.6�1.91 to 53.8�1.67. Therefore this study demonstrated that the Akt pathway is the more influential pathway in CB ability to induce a neuroprotective effect.

Rights

This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.

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