Decreased ketone oxidation in the somatosensory nervous system may be an important factor driving some of the neurological symptoms commonly seen in Friedreich ataxia (FA), according to a study published in Experimental Neurology. 

Ketolysis is known to play an integral role in the proper functioning of the nervous system. However, scientists are less sure about its specific role in the health of the somatosensory nervous system. Mice studies indicate that molecules responsible for ketone metabolism are downregulated in neurological diseases such as amyotrophic lateral sclerosis and FA. 

The authors of the study sought to further explore the relationship between ketone metabolism and the somatosensory nervous system, hypothesizing that ketone metabolism is critical for somatosensory nervous system development. To do so, they generated sensory neuron-specific, Advillin-Cre knockout of succinyl-CoA 3-oxoacid CoA-transferase 1 (Adv-KO-SCOT) mice. 

The research team conducted a series of measurements in these mice, such as assessing cutaneous and proprioceptive sensory behavior. Upon euthanization, histological studies were conducted for the purpose of dorsal root ganglia SCOT detection and sensory neuronal population assessment. In addition, they sought to quantify intraepidermal nerve fibers, myelination, and spinal dorsal horn innervation. 

Read more about FA etiology 

The authors found that Adv-KO-SCOT mice had near-total ablation of SCOT in the dorsal root ganglia neurons. In addition, this group of mice had larger peptidergic and neurofilament-heavy dorsal root ganglia soma compared with wild-type mice. The research team also reported that myelination aberrations were present in Adv-KO-SCOT mice, although mechanical and thermal sensitivity remained largely unaltered. 

“Overall, these findings suggest that ketone oxidation is essential for the normal development of sensory axons, highlights the deleterious effects of deficient ketone metabolism during development and provides a new link to possible mechanisms leading to sensory dysfunction in patients with Friedreich ataxia,” the authors concluded. 


Enders J, Jack J, Thomas S, et al. Ketolysis is required for the proper development and function of the somatosensory nervous systemExp Neurol. Published online March 30, 2023. doi:10.1101/2023.01.11.523492