Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease.
Sina K StumpfStefan A BerghoffAndrea TrevisiolLena SpiethTim DükingLennart V SchneiderLennart SchlaphoffSteffi Dreha-KulaczewskiAnnette BleyDinah BurfeindKathrin KuschMiso MitkovskiTorben RuhwedelPhilipp GuderHeiko RöhseJonas DeneckeJutta GärtnerWiebke MöbiusKlaus-Armin NaveGesine SaherPublished in: Acta neuropathologica (2019)
Pelizaeus-Merzbacher disease (PMD) is an untreatable and fatal leukodystrophy. In a model of PMD with perturbed blood-brain barrier integrity, cholesterol supplementation promotes myelin membrane growth. Here, we show that in contrast to the mouse model, dietary cholesterol in two PMD patients did not lead to a major advancement of hypomyelination, potentially because the intact blood-brain barrier precludes its entry into the CNS. We therefore turned to a PMD mouse model with preserved blood-brain barrier integrity and show that a high-fat/low-carbohydrate ketogenic diet restored oligodendrocyte integrity and increased CNS myelination. This dietary intervention also ameliorated axonal degeneration and normalized motor functions. Moreover, in a paradigm of adult remyelination, ketogenic diet facilitated repair and attenuated axon damage. We suggest that a therapy with lipids such as ketone bodies, that readily enter the brain, can circumvent the requirement of a disrupted blood-brain barrier in the treatment of myelin disease.
Keyphrases
- blood brain barrier
- mouse model
- cerebral ischemia
- physical activity
- weight loss
- white matter
- end stage renal disease
- spinal cord injury
- randomized controlled trial
- magnetic resonance
- chronic kidney disease
- newly diagnosed
- resting state
- prognostic factors
- patient reported outcomes
- stem cells
- mesenchymal stem cells
- functional connectivity
- bone marrow
- brain injury