ACSS2 mediates prenatal alcohol exposure-related morphological and behavioral phenotypes

Area of Science:

• Neuroscience
• Biochemistry
• Developmental Biology

Background:

• The enzyme Acetyl-CoA Synthetase 2 (ACSS2) regulates alcohol-related molecular and behavioral changes.
• The role of ACSS2 in prenatal alcohol exposure (PAE) is currently unknown.

Purpose of the Study:

• To investigate the role of ACSS2 in mediating PAE-related phenotypes.
• To identify the developmental timing of ACSS2 nuclear translocation in the developing brain.

Main Methods:

• Proteomic, genomic, and behavioral analyses in mouse models.
• Genetic engineering to create ACSS2-deficient mice.
• Assessment of histone acetylation and gene expression changes.

Main Results:

• ACSS2 translocates to the nucleus during in utero brain development.
• Alcohol-derived acetate is incorporated into fetal brain histone acetylation.
• Loss of ACSS2 attenuated PAE-induced craniofacial abnormalities, motor deficits, and cognitive impairments.
• ACSS2 deficiency prevented long-lasting chromatin and gene expression changes in the hippocampus and cerebellum.

Conclusions:

• ACSS2 is a key mediator of PAE phenotypes.
• Alcohol-derived acetate influences fetal brain epigenetics via ACSS2.
• Targeting ACSS2 may offer therapeutic strategies for PAE-related disorders.