Differential Regulation of Cholesterol-Related Gene Expression by HDAC Inhibition in Neuron-Enriched and Glia-Enriched Rat Primary Cultures
- 1Laboratory of Cellular Neurobiology of Learning, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia
Abstract
Brain cholesterol homeostasis is a highly sophisticated, epigenetically regulated process where neurons and glia play distinct roles in maintaining metabolic balance. Disruption of this tightly regulated system is a hallmark of many neurological disorders, including Alzheimer’s disease. Histone deacetylase (HDAC) inhibitors were shown to regulate transcription of metabolic genes in the brain. However, their influence on cholesterol-related gene expression in functionally different neural cell populations remains insufficiently characterized. In this study, we used a model of rat primary cultures enriched in either neurons or glial cells to compare the culture-specific transcriptional responses induced by the HDAC inhibitor trichostatin A (TSA). Using quantitative PCR, we analyzed the relative mRNA expression of representative genes involved in cholesterol synthesis (Hmgcs1, Mvd, Lss, Dhcr7), transport (Apoe, Apod), uptake (Vldlr, Ldlr), efflux (Abca7, Abcg1), and elimination (Cyp46a1). Our results suggest that HDAC inhibition induces complementary yet distinct and epigenetically tunable transcriptional responses in the neuronal and glial cell cultures maintained under their respective culture-specific conditions. We hypothesize that these transcriptional changes may have functional consequences for cholesterol metabolic pathways, including altered cholesterol accumulation in both cell types and enhanced cholesterol efflux in neurons. However, this requires further experimental validation. Overall, our results provide a framework for understanding how cell-type-specific epigenetic regulation of cholesterol-related genes may shape brain lipid homeostasis. These insights may facilitate the development of cell-targeted epigenetic therapies for neurological disorders associated with metabolic dysfunction.
Related
- A randomized study comparing plant sterol- and soluble fiber-enriched soymilk with plain soymilk in adults with elevated LDL cholesterol
- Medicarpin suppresses gastric cancer growth in association with inhibition of mevalonate pathway-associated cholesterol biosynthesis
- Pear Peel–Enriched Residue Extract Attenuates Ethanol‐Induced Liver Injury Through Regulation of Antioxidant Signaling and Lipid Metabolism
- Cholesterol Metabolism Regulation by Native and Oxidized Low-Density Lipoprotein in a Liver Cell Line
- 418 B cell regulation of anti-PD-1 immune checkpoint inhibition
BibTeX
@article{samorodova2026differential,
title = {{Differential Regulation of Cholesterol-Related Gene Expression by HDAC Inhibition in Neuron-Enriched and Glia-Enriched Rat Primary Cultures}},
author = {Alevtina A. Samorodova and Alexander P. Beletskiy and Pavel M. Balaban and Anastasia A. Borodinova},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209231},
url = {https://www.mdpi.com/1422-0067/27/20/9231},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Differential Regulation of Cholesterol-Related Gene Expression by HDAC Inhibition in Neuron-Enriched and Glia-Enriched Rat Primary Cultures
AU - Alevtina A. Samorodova
AU - Alexander P. Beletskiy
AU - Pavel M. Balaban
AU - Anastasia A. Borodinova
PY - 2026
DA - 2026/10/17
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209231
UR - https://www.mdpi.com/1422-0067/27/20/9231
AB - Brain cholesterol homeostasis is a highly sophisticated, epigenetically regulated process where neurons and glia play distinct roles in maintaining metabolic balance. Disruption of this tightly regulated system is a hallmark of many neurological disorders, including Alzheimer’s disease. Histone deacetylase (HDAC) inhibitors were shown to regulate transcription of metabolic genes in the brain. However, their influence on cholesterol-related gene expression in functionally different neural cell populations remains insufficiently characterized. In this study, we used a model of rat primary cultures enriched in either neurons or glial cells to compare the culture-specific transcriptional responses induced by the HDAC inhibitor trichostatin A (TSA). Using quantitative PCR, we analyzed the relative mRNA expression of representative genes involved in cholesterol synthesis (Hmgcs1, Mvd, Lss, Dhcr7), transport (Apoe, Apod), uptake (Vldlr, Ldlr), efflux (Abca7, Abcg1), and elimination (Cyp46a1). Our results suggest that HDAC inhibition induces complementary yet distinct and epigenetically tunable transcriptional responses in the neuronal and glial cell cultures maintained under their respective culture-specific conditions. We hypothesize that these transcriptional changes may have functional consequences for cholesterol metabolic pathways, including altered cholesterol accumulation in both cell types and enhanced cholesterol efflux in neurons. However, this requires further experimental validation. Overall, our results provide a framework for understanding how cell-type-specific epigenetic regulation of cholesterol-related genes may shape brain lipid homeostasis. These insights may facilitate the development of cell-targeted epigenetic therapies for neurological disorders associated with metabolic dysfunction.
SN - 1422-0067
ER -