CMT 1A dietary fasting: (IF) alleviates the neuropathic phenotype in the Trembler J mouse model

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Neurobiol Dis. 2009 Apr;34(1):146-54.

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.