Repurposed dietary supplement tackles schizophrenia in mice
Scientists at the University of Tokyo, Japan, have chanced upon a dietary supplement that appears to treat mice with a genetic mutation that causes schizophrenia. The drug known as betaine – originally intended to treat those with an inherited metabolic disease called homocystinuria – works by safeguarding the construction of the cellular skeleton of neurons in the mice; the mice were found to exhibit normal behaviours after being treated with betaine.
Behind the body’s natural synthesis of betaine and schizophrenia is another gene called kif3b: the kif3b gene belongs to the kinesin superfamily of genes that play an important role in mammals by encoding for motor proteins that work together to transport materials throughout neurons by moving up and down the cell’s skeleton structure.
Mice with genetic mutations that leave them with just one functional copy of the kif3b gene tend to avoid social interactions and respond similarly to human schizophrenia patients to what’s known as a prepulse inhibition test, which subjects them to sudden, loud sounds after quieter sounds and measures how startled they are.
As the mice grew, the scientists supplemented their diets with three times the amount of betaine than they would normally consume, and found that they exhibited normal behaviour. To dig into the reasons behind this, the team observed mutant nerve cells featuring the kif3b mutation that could be seen to grow differently to the way normal, healthy neurons develop, forming an unusually high amount of branch-like structures called dendrites. These types of neurons have also been observed in brain samples donated by people with schizophrenia, as has a type of chemical damage called carbonyl stress.
This stress impacts a protein called CRMP2 and inhibits its ability to assemble key components of the neuron’s cellular skeleton, and a similar process was found to be at play in the kif3b mutant mice where the proteins were instead found to clump together.
However, because betaine is known to prevent carbonyl stress that leads to CRMP2 malfunction, the scientists believe that the supplement therefore clears the way for a healthy cellular skeleton to form, and for the kif3b proteins to perform their normal role of transporting materials throughout the neuron.
The team now hopes to carry out further investigations involving clinical studies that explore the potential of betaine supplements as a schizophrenia treatment. Working in its favor is the fact that the drug is already considered safe for human consumption.
Read: Breakthrough UK study finds lack of key brain protein affects schizophrenia
Category: Features, Pharmaceuticals
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