Work

Differential Regulation of Cholesterol-Related Gene Expression by HDAC Inhibition in Neuron-Enriched and Glia-Enriched Rat Primary Cultures

Year: 2026

Type: article

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.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27209231

Authors: Alevtina A. Samorodova, Alexander P. Beletskiy, Pavel M. Balaban, Anastasia A. Borodinova

Institutions: Russian Academy of Sciences, Institute of Higher Nervous Activity and Neurophysiology

Language: English

Topic: Cholesterol and Lipid Metabolism

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499