Low cholesterol is generally a good thing. But decreasing the amount of low-density lipoprotein—LDL, the "bad cholesterol"—is only one part of the body's equation for a healthy balance of lipids. And although lowering cholesterol can be good for the heart, it's not always great for the brain, which contains about a quarter of the body's cholesterol.
Recent research has shown that drugs that lower cholesterol, such as statins, might put some individuals at risk for cognitive problems. And a new study suggests that diabetes, which affects cholesterol synthesis in the liver, might also be changing the rate these compounds are made in the brain.
Researchers found that diabetic mice had less of the crucial cholesterol in the membranes around their neural synapses. "This has broad implications for people with diabetes," Ronald Kahn, of the Joslin Diabetes Center at Harvard Medical School and coauthor on the new study, said in a prepared statement. The results were published online November 30 in Cell Metabolism.
"Since cholesterol is required by neurons to form synapses with other cells, this decrease in cholesterol could affect how nerves function," Kahn said. Affected systems could include "appetite regulation, behavior, memory and even pain and motor activity," he said. They correlate with increased risk of diabetic patients for eating disorders, depression and memory trouble.
For the study, Kahn and his team created mice that lacked sufficient insulin—to mimic a diabetic condition. In particular, the scientists targeted a gene known as SREBP-2 (which controls cholesterol metabolism) and other brain-based genes, causing the mice to produce—and retain—less cholesterol in key structures in the brain.
"These effects occurred in both the neurons and supporting 'glial' cells that helped provide some nutrients to the neurons," Kahn said. "Ultimately this affects the amount of cholesterol that can get into membranes of the neuron, which form the synapses and the synaptic vesicles."
When the diabetic mice received insulin injections, their genes seemed to return to normal functioning. The researchers noted that longer-term insulin depletion might cause more permanent damage to the myelin sheaths, the fatty covering of nerves that contain more than two thirds of the central nervous system's cholesterol and are crucial to neural communication.
"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 the body comes from," Kahn said. "But nobody had ever suspected that insulin and diabetes would play an important role in cholesterol synthesis in the brain."
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