Targeting mitochondria in neurons may help relieve severe forms of MS
Modifying cerebrospinal fluid to treat MS
People with the most severe forms of multiple sclerosis often have dysfunctional mitochondria in their neurons. Changing the composition of the cerebrospinal fluid may be a new way to address this problem and may one day help to treat this disease.
Dysfunctional mitochondria
Since the brain is immersed in cerebrospinal fluid, it is logical to think that MS can be treated by modifying this fluid, said Patrizia Casaccia of City University in New York in a statement.
To test this approach, she and her colleagues collected cerebrospinal fluid from people with intermittent attacks of MS symptoms - called relapsing-remitting MS - and from 29 people with progressive and more severe forms of the disease.
The team then placed rat neurons in these cerebrospinal fluid samples and used a fluorescent tracer to see the behaviour of mitochondria in these neutrons.
Elongated mitochondria
Mitochondria produce energy and are like the power plants of cells. When the team filmed the mitochondria of the rats, they found that they lay down when exposed to the fluid of people with progressive MS. But she didn't see the same thing when they were in the fluid of people with relapsed MS.
These elongated mitochondria produce less energy than normal mitochondria and eventually kill neurons. Previous research had shown that mitochondria elongate to produce more energy when there is a greater demand for or low availability of glucose.
The team found that cerebrospinal fluid from people with progressive MS had high levels of ceramides, a type of fatty acid. Exposing neurons to ceramides was sufficient to elongate their mitochondria in the same way as when they were exposed to cerebrospinal fluid from people with progressive MS.
Modify the cerebrospinal fluid
"We also discovered that ceramides induce neural damage by acting on two cellular mechanisms," Maureen Wentling of the Icahn School of Medicine on Mount Sinai in New York said in a statement. "On the one hand, ceramides have altered the ability of neurons to produce energy by directly damaging mitochondria. On the other hand, they also forced neurons to absorb glucose more quickly to provide energy to cells.
The team was able to compensate for this neurotoxic effect by adding glucose to the cerebrospinal fluid. They say that this is not a sustainable approach for people with multiple sclerosis, but that their results could lead to new therapies.
