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Study results may explain some diabetic effects on the brain









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LeDon Bean, graduate student, UNMC pharmacology and experimental neuroscience, was first author a study team that found a potential explanation for some of the effects of diabetes on the central nervous system.

A UNMC research team has found a potential explanation for some of the effects of diabetes on the central nervous system.

The discovery, which is reported in the Oct. 18 edition of Brain Research, could potentially explain the adverse affects of diabetes on parts of the brain that regulate bodily functions and sometimes, learning and memory.

To study the effects of diabetes on the brain, the research team looked at N-Methyl-D-Aspartate (NMDA) receptors in rats with type 1 diabetes.

“These receptors are involved with many brain functions, such as hypothalamus regulation, cell migration and synaptic formation, and they’re also involved with learning and memory,” said LeDon Bean, a UNMC pharmacology and experimental neuroscience graduate student and first author of the study.

Of the two subtypes of NMDA receptor subunits, NR1 and NR2, the research team studied NR2. There are four different kinds of NR2 subunits: NR2A, NR2B, NR2C and NR2D. In the diabetic brain, the team found that there was a decrease in the number of both NR2A and NR2B subunits in some regions of the brain.

“What we’re seeing is that specific subunits are being decreased,” Bean said. “But the question is twofold: why and what is the functional consequence? That’s an area for future research.”

The team found a reduction in the number of NMDA receptors in the untreated diabetic brain as compared to the non-diabetic brain, Bean said.

Since these receptors are involved with hypothalamic function, cognitive processes and other neuronal activities, the decrease in the number of receptors is significant.

“These receptors are necessary for learning and memory,” he said, “and so when you have a reduction of them as a result of the disease diabetes, that adversely affects learning and memory.”

“There has been a controversy as to whether these receptors change in diabetes,” said Daniel Monaghan, Ph.D., a professor of pharmacology and experimental neuroscience and principal investigator of the study. “But our work showed that select brain regions are especially vulnerable to the diabetes-induced changes and that these regional variations may account for the prior controversy.”

Bean and Dr. Monaghan’s work deserves to be lauded, said Tom Rosenquist, Ph.D., UNMC vice chancellor for research.

“Together, LeDon Bean and Dr. Monaghan have designed and carried out an excellent research study. The UNMC research community is very pleased and proud of their accomplishment,” Dr. Rosenquist said. “LeDon Bean is an outstanding graduate student.”

In addition to Bean and Monaghan, other UNMC participants included Hong Zheng, M.D., Ph.D., UNMC research associate, cellular and integrative physiology; and professor Kaushik P. Patel, Ph.D., cellular and integrative physiology.

Although the research team has not studied NMDA receptors in diabetic people, the information gained from the study might be helpful in explaining the adverse effects of diabetes on brain function in humans.

“Sometimes there is a huge jump from an animal model to a human model, but other groups have reported changes in learning and memory in some diabetic patients,” Bean said. “Thus there seems to be a consistency with respect to what we see in the rat model and the human model.”

Diabetes is a disease in which the body does not produce insulin or cannot use it properly. Insulin is needed to metabolize carbohydrates and regulate glucose levels in the blood. There are two types of diabetes: type 1 and type 2. Type 1 diabetes occurs when the body does not produce insulin. Type 2 diabetes occurs when the body does not produce enough insulin or ignores the insulin altogether.

The American Diabetes Association reports that 20.8 million children and adults in the United States, or 7 percent of the population, have diabetes. Diabetes is the fifth-deadliest disease in the United States.