Characterization of mitochondria-associated ER membranes in the enteric nervous system under physiological and
Giada Delfino1, Jean Baptiste Briand1, Thibauld Oullier1
1Nantes Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Nantes, The Enteric Nervous System in Gut and Brain Disorders, Nantes, France.
Abstract:
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.
Insights
Mitochondria-associated ER membrane (MAM) contacts in enteric neurons are identified and altered in a neurodegeneration model. This discovery offers new insights into the gut-brain axis in aging and disease.
Area of Science:
- Neuroscience
- Cell Biology
- Gastroenterology
Background:
- Endoplasmic reticulum (ER)-mitochondria associations, known as mitochondria-associated ER membranes (MAMs), are implicated in neurodegenerative diseases.
- The role of MAMs in the enteric nervous system (ENS) and their connection to the gut-brain axis in neurodegeneration remains largely unstudied.
Purpose of the Study:
- To characterize MAMs in enteric neurons of the distal colon in wild-type and senescence-accelerated mouse prone 8 (SAMP8) models.
- To investigate the functional implications of MAM alterations on calcium homeostasis in enteric neurons.
Main Methods:
- Utilized wild-type C57BL/6J and SAMP8 mice to study MAMs in distal colon enteric neurons.
- Established primary cultures of enteric neurons for functional analysis of MAMs.
- Assessed calcium homeostasis in cultured enteric neurons.
Main Results:
- Demonstrated the widespread presence of MAMs in enteric neurons for the first time.
- Observed altered MAM associations in SAMP8 mice compared to controls.
- Identified dysregulated calcium homeostasis in SAMP8 enteric neurons, suggesting functional MAM impairment.
Conclusions:
- Provides the first comprehensive characterization of MAMs in the ENS under physiological and neurodegenerative conditions.
- Suggests that altered enteric MAMs may contribute to age-related neurodegeneration via the gut-brain axis.
- Highlights the potential of enteric MAMs as a novel target for understanding and treating neurodegenerative disorders.
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