Researchers Used Multiphoton Microscopy to Measure Protein Translation

Scientists at the University of Pennsylvania School of Medicine have discovered a pattern to protein manufacture in the hippocampus, the part of the brain devoted to making memories.

Christy Job, PhD, a postdoctoral neurobiologist with James H. Eberwine, PhD, Professor of Pharmacology at Penn, measured a protein as it was being made in structures of brain cells called dendrites. "The patterns of electrical stimulation which make memories are well-established, but how those memories are stored is still unexplained," said Job. "We decided to tackle this from a completely different angle by looking at protein synthesis in dendrites."

Job and Eberwine grew particular cells from the hippocampus called neurons that extend long structures (dendrites) away from the main portion of the cell, known as the cell body. Cell bodies store the genetic code (the DNA) so a message, mRNA, which is made from the DNA, moves from the cell body to dendrites.
Using a procedure known as multiphoton microscopy, Job and Eberwine were able to measure translation of this message into a protein that fluoresces. Multiphoton microscopy enabled them to examine the pattern of fluorescence across space and time.

"We thought that the rate of translation might be different in dendrites, but not only was it exponentially faster than translation in the cell body, it was also faster at particular places in each dendrite," Eberwine said.

The research, which will be published in the journal Proceedings of the National Academy of Science on October 23, could have important implications for other research into how memories are stored in the brain. Neuronal dendrites are known to pick up and convey information in the form of electrical pulses, but they could also store information by synthesizing proteins from mRNA templates.

"This raises the possibility that there is a pattern or code in the order of translation and mechanics of the translational process that exists in these translation sites at the dendritic level for the formation of memories," Eberwine said. "It could also be important for illnesses involving memory loss or mental retardation, such as Alzheimers and fragile X retardation."

The study was funded by the National Institutes of Health.


////////////////


Editor's note: Eberwine may be reached directly at: 215-898-0420.


///////////////

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.