Multi-Omic Epigenetic-Based Model Reveals Key Molecular Mechanisms Associated with Palmitic Acid Lipotoxicity in Human Astrocyte

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

Neurotoxicity

Neurotoxins are natural or chemical compounds that can disturb the neurological system of mammals. The neurotoxic potential of a neurotoxin is a consequence that may occur if tissue concentrations surpass a particular threshold. Chemicals disrupt adult brain function by interfering with the structure and function of various neuronal pathways, circuits, and systems in diverse ways. Neurotoxicity - New Advances provides updated information about neurotoxicity and neurotoxic chemicals including nanomaterials and pesticides. It also discusses prevention and treatment strategies. This book is an instructive and valuable guide to understanding neurotoxicity and identifying neurotoxicity mechanisms and neurotoxic disorders