People with the more severe forms of multiple sclerosis are known to have dysfunctional mitochondria in their neurons. Altering the make-up of spinal fluid could be a new way to address this, and may one day help treat the disorder.
Because the brain is bathed in cerebrospinal fluid, it makes sense to see whether MS can be treated by altering this fluid, said Patrizia Casaccia at The City University of New York in a statement. To test this approach, she and her colleagues took spinal fluid from people who experience intermittent attacks of MS symptoms 鈥� known as relapsing or remitting MS 鈥� and 29 people with more severe, progressive forms of the condition.
The team then put rat neurons in these spinal fluid samples and used a fluorescent tracer to see how the mitochondria in those neutrons behaved.
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Elongated mitochondria
Mitochondria produce energy, and are known as the powerhouses of cells. When the team videoed the rat mitochondria, they saw they elongated when exposed to fluid from people with progressive MS. They didn鈥檛 see the same thing when in fluid from people with relapsing MS.
These elongated mitochondria produced less energy than normal ones, eventually killing the cell. Previous research has indicated that mitochondria elongate in an effort to produce more energy when there is more demand or less glucose available.
The team found that the spinal fluid from people with聽progressive MS聽had raised levels of ceramides, a type of fatty acid. Exposing neurons to ceramides turned out to be enough to make their mitochondria elongate in the same way as when exposed to spinal fluid from people with progressive MS.
Altering spinal fluid
鈥淲e further discovered that ceramides induced neuronal damage by acting on two cellular mechanisms,鈥� said Maureen Wentling at the Icahn School of Medicine at Mount Sinai in New York in a statement. 鈥淥n one end, ceramides impaired the ability of neurons to make energy by directly damaging the mitochondria. On the other end, they also forced neurons to more rapidly uptake glucose in an attempt to provide energy for the cell.鈥�
The team was able to offset this neurotoxic effect by adding glucose to the spinal fluid. They say this isn鈥檛 a sustainable approach for people with MS, but that their findings could lead to new therapies.
Brain
