Janneth Gonzalez

By George E. Barreto, Janneth Gonzalez, Francisco Capani and Ludis Morales

Part of the book: Neurodegenerative Diseases

By Ricardo Cabezas, Marco Fidel Avila, Daniel Torrente, Ramon Santos El-Bachá, Ludis Morales, Janneth Gonzalez and George E. Barreto

Part of the book: Neurodegenerative Diseases

By Felipe Rojas-Rodríguez, Andrés Pinzón, Daniel Fuenmayor, Tábata Barbosa, Diego Vesga Jimenez, Cynthia Martin, George E. Barreto, Andrés Aristizabal-Pachón and Janneth Gonzalez

Astrocytes are critical for the metabolic, structural and functional modulatory support of the brain. Lipotoxicity or high levels of saturated fatty acid as Palmitate (PA) has been associated with neurotoxicity, the loss or change of astrocytic functionality, and the etiology and progression of neurodegenerative diseases such as Parkinson or Alzheimer. Several molecular mechanisms of PA’s effect in astrocytes have been described, yet the role of epigenetic regulation and chromatin architecture have not been fully explored. In this study, we developed a multi-omic epigenetic-based model to identify the molecular mechanisms of lipotoxic PA activity in astrocytes. We used data from nine histone modifications, location of Topological Associated Domains (TADs) and transcriptional CTCF regions, where we identified the basal astrocyte epigenetic landscape. Moreover, we integrated transcriptomic data of astrocytic cellular response to PA with the epigenetic multi-omic model to identify lipotoxic-induced molecular mechanisms. The multi-omic model showed that chromatin conformation in astrocytes treated with PA have response genes located within shared topological domains, in which most of them also showed either repressive or enhancing marks in the Chip-Seq enrichment, reinforcing the idea that epigenetic regulation has a huge impact on the lipotoxic mechanisms of PA in the brain.

Part of the book: Neurotoxicity