AsianScientist (Sep. 6, 2017) – In a study published in The Journal of Clinical Investigation, researchers from Osaka university in Japan have discovered that a growth factor produced by the pancreas promotes the regeneration of the myelin sheath in neurons.
Brain functions are maintained by the neural network, which requires neurons to be wrapped by a lipid coat known as the myelin sheath. Demyelination is detected in the patients suffering from diseases such as multiple sclerosis and is associated with neurological dysfunctions.
In normal development, oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes, which are required for myelination. OPCs will proliferate around the lesions of demyelination after injury and contribute to spontaneous remyelination. However, the molecular mechanism of OPCs proliferation is not fully understood.
In this study, a team led by Associate Professor Rieko Muramatsu from Osaka University revealed that breaches in the blood brain barrier in the vicinity of brain lesions allowed growth factors to enter the brain and promote OPC proliferation at the site of injury.
The team suspected that with the breach, factors from peripheral organs secreted into the blood could now reach the brain. To test this hypothesis, the researchers disrupted the vascular barrier and myelin structures in mice by injecting a toxin, lysophosphatidylcholine (LPC). They then screened for circulating factors that promote OPCs proliferation, eventually identifying FGF21 as a candidate molecule. FGF21 is secreted by the pancreas and typically cannot enter the brain.
Mice treated with LPC showed high levels of FGF21 around demyelinated lesions leading, to remyelination. This was not observed in mutant mice that could not express FGF21. Other mice that received direct administration of FGF21 to demyelinated lesions caused by LPC injection also showed increased remyelination and better recovery of neurological function.
In addition, the researchers found that OPCs expressed higher levels of β-klotho, a co-receptor for FGF21, following LPC injection. Without expression of β-klotho, FGF21 could not promote remyelination.
“FGF21 is known to regulate metabolism, but its effects on OPC proliferation were unexpected,” said Muramatsu.
The results suggest that FGF21 has therapeutic potential for demyelinating diseases. FGF21 analogs are already being used for clinical studies on diabetes, which means their development for remyelination could proceed more quickly than an untested compound.
“There are many drugs that inhibit demyelination, but none that promote remyelination. FGF21 is a new candidate that deserves more testing. Most importantly, we showed that the peripheral milieu promotes central nervous system remyelination,” added Muramatsu.
The article can be found at: Kuroda et al. (2017) Peripherally Derived FGF21 Promotes Remyelination in the Central Nervous System.
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Source: Osaka University.
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