Biologist helps explain why cardiovascular health tends to vary by sex

A woman stands in front of a very large poster. She points to her name -- Minqian Shen -- within a long list of names. Visible text: ENDO. 2015 Abstract Awards and Travel Grants. Early Career Forum Travel Awards. Supported by the Endocrine Society. These application-based travel awards are presented to graduate students, medical students, postdoctoral fellows, and clinical fellows in endocrinology. 125 travel awards supported by the Society; 2 additional travel awards supported by Women in Endocrinology.

Minqian Shen, a graduate student of Dr. Haifei Shi, points to her name on a list of students who received Early Career Forum Travel Awards for the 2015 Endocrine Society Annual Meeting.

There are a number of reasons women tend to live longer than men. One of them is cardiovascular disease – on average, women develop it about a decade later than men. The female hormone estrogen seems to play a role, by keeping women’s arteries healthier until menopause. But Haifei Shi, an associate professor of biology at Miami University, thinks brain-derived neurotrophic factor (BDNF) may also play a role.

BDNF is a protein that helps sustain existing neurons and encourages the development of new neurons and synapses in the brain and central nervous system of humans and other mammals. In her lab, Shi has found that exposing rats to BDNF causes them to eat less and exercise more.

Assuming the same thing is true in humans, BDNF could one day be used in therapeutic treatments to help control obesity, which is a major risk factor for the development of cardiovascular disease.

But to develop safe and effective treatments, scientists need to better understand how BDNF works in the nervous system, and how it might work differently for male and female patients.

Shi is contributing to this understanding by studying rats. She has found that female rats are more sensitive to BDNF than male rats are. That is, it takes less BDNF to produce an advantageous ratio of food consumption to energy expenditure in a female rat than it takes to produce the same advantageous ratio in a male rat. She says this suggests that any BDNF-based drug therapies should be developed with gender-specific dosing in mind.

Dosing isn’t the only consideration, though. The route of delivery is also important. According to the FDA, there are some 100 ways of introducing a drug into the body, everything from auricular (by way of the ear) to oral (by way of the mouth) to subcutaneous (injected under the skin). The form a drug comes in – say, ear drops, pills, or injections – influences how quickly it is released into the system, how it is distributed throughout the system, and how quickly it is absorbed and eliminated. Those things can have a huge effect on the safety and efficacy of a specific treatment.

To determine the optimal route of delivery for a BDNF-based drug, Shi says it’s important to find the parts of neural circuit in the autonomic nervous system that BDNF activates, including brain nuclei, ganglia cells, and nerve terminals.

“If BDNF activates different parts of these neuralcircuits in males than in females,” she says, “then the targeting sites and route of delivery for any future drugs could be different as well.”

Shi plans to study this question using funds from a $390,150 grant she recently received from the National Institute of Diabetes and Digestive and Kidney Diseases, which is part of the National Institutes of Health (NIH).

“Given how difficult it is to receive funding from NIH right now, at first I was not sure if I could get funding,” Shi says. “When they sent me the award notice I felt very fortunate.”

She was also gratified to find that the program officer and every member of the NIH panel that reviewed her grant proposal characterized Miami’s research climate as excellent.

Contributing to that excellence, Shi says, are the research facilities and internal funding support provided by the Department of Biology, the College of Arts and Science (CAS), and the University Senate’s Committee for Faculty Research (CFR). She has received the Madalene and George Shetler Diabetes Research Award from the CAS and two CFR Faculty Research Grants – one in AY2009-2010 and one in AY2013-2014. These awards helped her gather preliminary data that enabled her to demonstrate the potential of her work in applications to the NIH and other funding agencies, including the American Heart Association.

Shi’s most recent NIH grant uses the R15, or Academic Research Enhancement Award (AREA), mechanism. Consistent with this program’s goal to expose students to research, Shi plans to involve students in all aspects of her current study, just as she did with a previous AREA grant study. Graduate students Xian Liu, Minqian Shen, and Qi Zhu and undergraduate students Annie Davis and Anjali Prior will help design, troubleshoot, and carry out experiments. They will collect data, run analyses, write manuscripts, and present results at local, national, and international conferences.

Davis, a sophomore double majoring in premedical studies and public health, attended the international meeting of the Society for the Study of Ingestive Behavior with Shi and graduate students Xian and Minqian in Denver this past July.

“Annie learned so much. I think it was really good exposure for her,” Shi says. “In the future, I’d like to take more students to this and other conferences.”

Given Shi’s continued success, not only in doing research, but also in securing funding to support it, that seems a likely prospect.

Written by Heather Beattey Johnston, Associate Director & Information Coordinator, Office for the Advancement of Research & Scholarship, Miami University.

Photo of Xian Liu, Haifei Shi, and Minqian Shen courtesy of Haifei Shi. Photo of Minqian Shen courtesy of Haifei Shi.

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