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Brain changes in diabetic mellitus contribute to neuropathy complications

by Carolyn Lacey , 25 July 2016.


Diabetes Mellitus is a growing global health crisis. According to the World Health Organization 150 million people have diabetes mellitus worldwide- and they predict this will double by year 2025.

You might be asking why a neuroscience blog might be concerned with diabetes? After all, isn’t it a disorder of blood sugar levels? The problem with diabetes- on top of all the symptoms associated with the metabolic dysfunction- is that long-term diabetic patients can develop further complications of their nervous systems such as vision problems and nerve damage.

Hand of the child in a hand of mother

Diabetic Neuropathy (nerve damage) affects over half of diabetic patients – the most common complication of diabetes. Often described as “tingling pain”- it can lead to pain, hypersensitivity to tactile stimulation, numbness, sensory loss, limb damage (because loss of feeling can lead to damage that sometime require amputation) and impotence in diabetic men. As well as being debilitating, diabetic neuropathy is also costly: an estimated 27% of diabetes health-care costs (Kelsey Juster-Switlyk and A. Gordon Smith; see reading list).

Diabetic Neuropathy is especially prominent in cases where diabetes that is not well controlled, over 40s, overweight people or in those who have suffered for a long time. It can occur in Type I and Type II diabetes. For these reasons, if you suffer from diabetes then regular foot and eye checks are essential.

Although peripheral nerve damage in diabetes has long been recognized as a factor in diabetic neuropathy- less is known about the role of the brain in altered processing of sensory information (such as pain) during nerve damage. New research published in the European Journal of Neuroscience from the lab of Natalie Gardener and Rasmus Peterson at the University of Manchester, UK, has discovered that the brain plays a big role in abnormal sensory processing that develops as a complication of diabetes.

Using rats that show diabetes, the researchers found that after 12 weeks of diabetes the rats had heightened sensitivity to nerve stimulation- such as touching the paw. Yet, interestingly, they did not find any change to the nerves that were carrying the messages of sensation to the brain (peripheral nerves)- instead they found an amplification of the signals in the part of a brain called the thalamus that processes this information. To investigate this the researchers studied the responses in the thalamus to touching the whiskers of the rat.

Rat whiskers are very interesting- they are basically the equivalent of our fingertips and are just as sensitive to touch. Rats use their whiskers a lot to navigate their environment (one reason that blind rats do not seem “blind” when they are moving about- makes sense as they are nocturnal!). Due to this whisker prowess, rat brains have highly specialized areas of the brain that respond to each whisker stimulation. In terms of research these whisker systems are really useful as they are highly stereotyped- meaning they are almost identical in all rats.

The thalamus is a group of brain regions that are highly selective for function- some parts are important for sensation, others for motor, or vision for example- and these regions act as interpreters of information that needs to be analyzed for us to perceive and respond. A major staging point in the map system for each whisker in the brain is in the thalamus (specifically the ventral posterolateral thalamic nucleus).

By recording the electrical activity of the thalamus whisker detector brain cells in diabetic and healthy rats, the researchers discovered that these brain cells had higher baseline activity in diabetic rats and their responses to whisker movement were exaggerated, compared to healthy rats. And, moreover, these changes were not due to an enhanced signal from the peripheral nerves. It’s like the thalamus whisker detector cells have “gone rogue”.

This suggests that symptoms of diabetic neuropathy, like pain, could have roots in the way the brain interprets peripheral (outside of brain) nerve information- the mechanisms behind this need to be examined. Prof. Tom Salt (CSO of Neurexpert and expert on thalamus and pain systems) commented, "This study highlights the importance of brain networks in pain conditions that are often thought of as being of peripheral origin. Studying neural activity in such brain networks should open up new avenues to treating conditions such as diabetic and other neuropathies".

As diabetic neuropathy is incurable, costly, debilitating and so common a complication to diabetes- this result is a new avenue for therapeutic advancement, understanding and control of neuropathy for suffering diabetic patients.


To view the original open access paper discussed in this blog:

“Thalamic amplification of sensory input in experimental diabetes” in European Journal of Neuroscience click here.


Other reading sources:


Kelsey Juster-Switlyk and A. Gordon Smith: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847561/pdf/f1000research-5-8502.pdf





The Blog was written by Carolyn Lacey, Scientific Outreach Manager at Neurexpert. To learn more about Carolyn and Neurexpert, please click here.


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