November 30, 2010

Diabetes Affects Brain Cholesterol

Researchers at Joslin Diabetes Center have discovered that diabetes is able to affect how much cholesterol the brain is able to produce.

Scientists have discovered that brain cholesterol synthesis, which is the only source of cholesterol for the brain, dropped in several mouse models of diabetes. 

"Since cholesterol is required by neurons to form synapses (connections) with other cells, this decrease in cholesterol could affect how nerves function for appetite regulation, behavior, memory and even pain and motor activity," says Dr. Kahn, who is also Mary K. Iacocca Professor of Medicine at Harvard Medical School.  "Thus, this has broad implications for people with diabetes."

Kahn wrote in the journal Cell Metabolism that other research has found that people with diabetes may display varying types of alterations in brain function or ways of responding to stress.

"It is well known that insulin and diabetes play an important role in regulating cholesterol synthesis in the liver, where most of the cholesterol circulating in blood comes from," Kahn adds. "But nobody had ever suspected that insulin and diabetes would play an important role in cholesterol synthesis in the brain."

If the brain does not produce enough cholesterol, then it can lead to Alzheimer's disease and other neurodegenerative conditions.

The newly discovered mechanism may help play a role in diabetic neuropathy, which still remains a large challenge for therapy.

People with diabetes are also known to suffer from depression, memory loss and eating disorders. 

The researchers examined gene expression in the hypothalamus of a mouse with type-1 diabetes.  They found decreased expression for almost all of the genes of cholesterol synthesis, including a gene called SREBP-2, which acts as a master regulator for cholesterol production. 

The team also discovered that similar findings were present in the cerebral cortex and other regions of the brain in these animals. 

This phenomenon was associated with decreased cholesterol synthesis.  Treating the mice with insulin helps to reverse the process.

"Our studies showed that these effects occurred in both the neurons and supporting 'glial' cells that help provide some nutrients to the neurons," Kahn wrote. "Ultimately this affects the amount of cholesterol that can get into the membranes of the neuron, which form the synapses and the synaptic vesicles"”the small structures that contain neurotransmitters."

He said that the results raise the prospect that cholesterol-lowering statins might have unintended consequences for the brain and its function.  The researchers said that earlier studies designed to look for a potential effect of statins on cognitive function in patients have yielded conflicting results.


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