brittle deformation

Scientists track down possible new treatment for epilepsy

Increasing the concentration of specific fats in the brain could suppress epileptic seizures. This is evident from ground-breaking research carried out by the research groups of Professor Patrik Verstreken (VIB-KU Leuven) and Professor Wim Versées (VIB-Vrije Universiteit Brussel). The results of their close collaboration have been published in the leading trade journal Nature Structural & Molecular Biology.

Professor Patrik Verstreken specializes in brain research, focusing on synapses. These are the junctions between two nerve cells where electrical signals are transmitted. In various brain disorders — such as Parkinson’s disease — there is impaired communication at these synapses.

Professor Wim Versées examines the processes which take place in our cells, right down to the level of individual molecules and atoms. By figuring out the three-dimensional structures of protein molecules, he tries to obtain crucial information about their role in the cell and the mechanisms which underlie various disorders.

The key role of TBC1D24
In earlier research involving fruit flies, Professor Verstreken had already demonstrated that a protein known as ‘Skywalker’ plays a crucial role in maintaining communication between brain cells. An almost identical protein operates in the human brain under the name ‘TBC1D24’.

Professor Patrik Verstreken (VIB-KU Leuven): “Genetic mutations of the protein TBC1D24 cause a deviation known as the DOOR syndrome. Alongside deafness, deformed nails, brittle bones and mental retardation, this serious genetic disorder is characterized by neurodegeneration, movement disorders and epilepsy.”

Analysis with atomic precision
By joining forces with Professor Wim Versées at the VIB research center for structural biology, the scientists were able to figure out the three-dimensional structure of Skywalker, making it possible to study the protein in microscopic detail.

Professor Wim Versées (VIB-Vrije Universiteit Brussel): “Looking at Skywalker in this way gave us completely new insights into the precise function of this protein, and therefore also the function of the human protein TBC1D24. Among other things, we discovered that it connects with specific brain fats. And more importantly, this connection is impaired in over 70% of patients with a TBC1D24 mutation.”

Suppression of epileptic seizures
On the basis of this discovery, the scientists increased the concentration of specific brain fats in fruit flies with a Skywalker mutation. What happened? The epileptic seizures in the sick fruit flies were completely suppressed.

Professor Patrik Verstreken (VIB-KU Leuven): “Our work shows that increasing specific brain fats at the synapses of patients with a TBC1D24 mutation is a possible strategy for preventing epileptic seizures. And although our work focuses on people with TBC1D24 mutations, we think that our findings could be relevant to various forms of epilepsy.”

Scientific cross-pollination
Professor Wim Versées (VIB-Vrije Universiteit Brussel): “Our two research groups will now continue to collaborate in order to seek out strategies for increasing the concentration of specific fats in the brain to prevent epileptic seizures. This research stems from cross-pollination between structural biology, biochemistry and genetics, so we will certainly continue down this interdisciplinary route.”

UV Light & Calcium Metabolism

UV light is a mysterious substance that many reptile keepers hear about but don’t really understand. Humans cannot see it and so a UV light looks pretty much like any other to us, so why is it so important?

There are three main “types” of UV light: UVA, UVB, and UVC. They are all different because they are composed of different wavelengths. Sunlight is composed of all three of these and UVA and UVB are present in different amounts depending on location on the earth, time of day, season, etc.

UVA is produced by regular full spectrum bulbs in varying amounts. Reptiles can see in the UVA spectrum and when they are supplied with it they seem to have better appetites, breed more often, and behave more like they do in the wild. UVB is needed by reptiles to produce vitamin D3 and aids in calcium metabolism. UVC is harmful to cells and is actually used in germicidal lamps for destroying bacteria and viruses, this is filtered out by our ozone layer.

Cells in reptile skin produce pro vitamin D which is a pre-precursor of D3. The body cannot use this pro vitamin without changing it. When the pro vitamin is “hit” with UVB rays it is changed into previtamin D3. This previtamin is slowly changed to vitamin D3 but only if the skin is warm. D3 is released from cells and picked up by special proteins in the blood that carry it to the liver.

In the liver D3 is converted  into calcidiol. Calcidiol travels all over the body and does many things. It supports the immune system, cardiovascular system, and pretty much any other organ system and allows them to function properly. Calcidiol also plays a role in preventing cells from becoming cancerous.

Calcidiol is taken up by the kidneys and changed into calcetriol which controls how much calcium is taken up by the intestines and also put back into circulation by the bones.

Calcium is used by the body as needed and any extra is stored in the bones.This is where metabolic bone disease comes into play. MBD is a lay term for any number of diseases involving calcium metabolism but the most common is nutritional secondary hyperparathyroidism. If a reptile is not getting enough calcium, its parathyroid gland will secrete parathyroid hormone which tells the bones to release calcium into the blood stream for use. If calcium is still not available the body will continue sapping it from the bones and this causes them to become brittle and deformed.

Reptiles need UV light, calcium and heat to function correctly. An iguana that has plenty of UV rays and calcium in the diet but is kept too cool cannot convert previtamin D3 to D3 and it will not be able to absorb calcium. Another lizard kept at the right temperature and with plenty of calcium in the diet will still not be able to use it without UVB rays.

This is why poor husbandry is the main disease of reptiles. Some owners become impatient when I quiz them on their heat and lighting because they just want their reptile to be better. Almost always I find there is an inadequacy somewhere.