The role of Elovl5 in cerebellar synapses

Elongase of very long chain fatty acids-5 (ELOVL5) is a gene encoding for an enzyme involved in the biosynthesis of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). Downstream products of ELOVL5 include arachidonic acid and docosahexaenoic acid, from which endocannabinoids and other molecules with biological effects on the brain are produced. It has been demonstrated that ELOVL5 is ubiquitary expressed, with particularly high level in cerebellar Purkinje cells. Mutations in ELOVL5 gene cause spinocerebellar ataxia type 38 (SCA38). We decided to investigate the physiological effects of the lack of Elovl5. We used mice with a homozygous deletion of ELOVL5 that present ataxia and cerebellar atrophy similarly to patients with SCA38 and have been validated as animal model for this disease. Our results show that Purkinje cells basal activity and parallel fiber-Purkinje cell synaptic transmission are unaffected, as well as mGlu receptor expression and postsynaptic current. We also analyzed the climbing fiber-Purkinje cell synapse and the axon terminals in the deep cerebellar nuclei to further investigate Elovl5 role in the cerebellum. Patch-clamp recordings of Purkinje cells of Elovl5-/- mice revealed an impairment in the endocannabinoid-dependent short-term plasticity of the parallel fiber-Purkinje cells synapse. In conclusion, these results suggest that Elovl5 plays a crucial role in maintaining specific neuronal functions.