Characterisation of Mitochondria-associated ER membranes in the enteric nervous system under physiological and pathological conditions
Résumé
Alterations in endoplasmic reticulum-mitochondria associations and in mitochondria-associated ER membrane (MAM) behaviour have been reported in the brain in several neurodegenerative diseases. Despite the emerging role of the gut-brain axis in neurodegenerative disorders, the biology of MAM in the enteric nervous system (ENS) has not previously been studied. Therefore, we set out to characterise the MAM in the distal colon of wild type C57BL/6J mice and in senescence accelerated mouse prone 8 (SAMP8), a mouse model of age-related neurodegeneration. We showed for the first time that MAM are widely present in enteric neurons and that their association is altered in SAMP8 mice. We then examined the functions of MAM in a primary culture model of enteric neurons and showed that calcium homeostasis was altered in SAMP8 mice when compared to control animals. These findings provide the first detailed characterisation of MAM in the ENS under physiological conditions and during age-associated neurodegeneration. Further investigation of MAM modifications in the ENS in disease may provide valuable information about the possible role of enteric MAM in neurodegenerative diseases.