V-70
Disorders of the Nervous System
Nothobranchius furzeri: an emerging aging model to study alpha-synucleinopathy in the gut-brain axis.
Janina Borgonovo1,2,3,4, Danilo B. Medinas3,4,5, Marcela González6, Estela M. Muñoz1, Jorge M. Campusano6, Claudio Hetz2,3,4,7, Miguel L. Concha2,3,4
1. Institute of Histology and Embryology of Mendoza (IHEM), National University of Cuyo (UNCuyo), National Scientific and Technical Research Council (CONICET), Mendoza, Argentina.
2. Interdisciplinary Nucleus of Biology and Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
3. Biomedical Neuroscience Institute, Santiago, Chile.
4. Center for Geroscience, Brain Health and Metabolism, Santiago, Chile.
5. Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
6. Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
7. Buck Institute for Research on Aging, Novato, CA, USA.
Presenting Author:
janiborgonovo@gmail.com
Enteroendocrine cells (EECs) are key components of microbiota-gut-brain axis. EECs sense changes in the intestinal microenvironment and transmit signals to the central nervous system (CNS) through paracrine and neuronal pathways. EECs express synaptic proteins and possess axon-like basal processes that form synaptic contacts with vagal afferents. Given these neuronal features, EECs have been proposed as potential sites susceptible to neuronal-like abnormalities, including α-synucleinopathy. Here, we investigated whether physiological aging is accompanied by perturbations in EECs homeostasis and abnormal α-synuclein expression. We used the short-lived vertebrate Nothobranchius furzeri (Nf) to assess age-related changes in EECs. Aging was associated with loss of EECs homeostasis characterized by EECs hyperplasia and increased 5-hydroxytryptamine production. These alterations were accompanied by increased α-synuclein-expressing EECs and accummulation of α-synuclein in the myenteric plexus and the brain. These indicate that EECs are particularly susceptible to age-related changes that may alter intestinal physiology and gut-brain communication. The findings provide a foundation for exploring whether elevated α-synuclein in EECs may initiate peripheral proteinopathy with potential implications for the CNS. Furthermore, this work presents Nf as a valuable model for investigating the link between intestinal aging and neurodegenerative diseases.
