Contacting the gut: Mitochondria-associated Endoplasmic Reticulum Membranes in the Enteric Nervous System.

Changes in the connections between the endoplasmic reticulum (ER) and mitochondria, as well as alterations in mitochondria-associated ER membrane (MAM) signalling, have been documented in various neurodegenerative diseases affecting the brain. Despite the growing recognition of the significance of the gut-brain axis in neurodegenerative conditions, there has been no prior investigation into the biology of MAM within the enteric nervous system (ENS). Our recent research reveals, for the first time, the existence of connections between the ER and mitochondria within enteric neurons. Additionally, we observed alterations in the dynamics of these connections in the enteric neurons from a mouse model exhibiting age-related neurodegeneration. These findings provide the first detailed characterization of MAM in the ENS under physiological conditions and in a mouse model of age-associated neurodegeneration and shed new light on the potential role of enteric MAM in the context of neurodegenerative disorders.

Characterization of mitochondria-associated ER membranes in the enteric nervous system under physiological and pathological conditions.

Alterations in endoplasmic reticulum (ER)-mitochondria associations and in mitochondria-associated ER membrane (MAM) behavior 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 characterize the MAM in the distal colon of wild-type C57BL/6J mice and senescence-accelerated mouse prone 8 (SAMP8), a mouse model of age-related neurodegeneration. We showed for the first time that MAMs are widely present in enteric neurons and that their association is altered in SAMP8 mice. We then examined the functions of MAMs in a primary culture model of enteric neurons and showed that calcium homeostasis was altered in SAMP8 mice when compared with control animals. These findings provide the first detailed characterization of MAMs 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 MAMs in neurodegenerative diseases.NEW & NOTEWORTHY Our work shows for the first time the presence of contacts between endoplasmic reticulum and mitochondria in the enteric neurons and that the dynamic of these contacts is affected in these cells from an age-related neurodegeneration mouse model. It provides new insights into the potential role of enteric mitochondria-associated endoplasmic reticulum membrane in neurodegenerative disorders.

Oligodendroglial primary cilium heterogeneity during development and demyelination/remyelination.

The primary cilium (PC) has emerged as an indispensable cellular antenna essential for signal transduction of important cell signaling pathways. The rapid acquisition of knowledge about PC biology has raised attention to PC as a therapeutic target in some neurological and psychiatric diseases. However, the role of PC in oligodendrocytes and its participation in myelination/remyelination remain poorly understood. Oligodendrocyte precursor cells (OPCs) give rise to oligodendrocytes during central nervous system (CNS) development. In adult, a small percentage of OPCs remains as undifferentiated cells located sparsely in the different regions of the CNS. These cells can regenerate oligodendrocytes and participate to certain extent in remyelination. This study aims characterize PC in oligodendrocyte lineage cells during post-natal development and in a mouse model of demyelination/remyelination. We show heterogeneity in the frequency of cilium presence on OPCs, depending on culture conditions in vitro and cerebral regions in vivo during development and demyelination/remyelination. In vitro, Lithium chloride (LiCl), Forskolin and Chloral Hydrate differentially affect cilium, depending on culture environment and PC length correlates with the cell differentiation state. Beside the role of PC as a keeper of cell proliferation, our results suggest its involvement in myelination/remyelination.