Intermittent fasting alleviates the neuropathic phenotype in mouse model of CMT

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Neurobiol Dis. 2009 Apr;34(1):146-54.Related Articles, Links

Intermittent fasting alleviates the neuropathic phenotype in a mouse model of

Charcot-Marie-Tooth disease.

Madorsky I, Opalach K, Waber A, Verrier JD, Solmo C, T, Dunn WA Jr,

Notterpek L.

Department of Neuroscience, College of Medicine, McKnight Brain Institute,

University of Florida, Gainesville, FL 32610, USA.

Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of

peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of

the peripheral nervous system. In this study we asked whether dietary

restriction by intermittent fasting (IF) could alleviate the neuropathic

phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that

neuropathic mice kept on a five month long IF regimen had improved locomotor

performance compared to ad libitum (AL) fed littermates. The functional benefits

of this dietary intervention are associated with an increased expression of

myelin proteins combined with a thicker myelin sheath, less redundant basal

lamina, and a reduction in aberrant Schwann cell proliferation. These

morphological improvements are accompanied by a decrease in PMP22 protein

aggregates, and enhanced expression of cytosolic chaperones and constituents of

the autophagy-lysosomal pathway. These results indicate that dietary restriction

is beneficial for peripheral nerve function in TrJ neuropathic mice, as it

promotes the maintenance of locomotor performance.