ACSS2 mediates prenatal alcohol exposure-related morphological and behavioral phenotypes

Area of Science:

• Neuroscience
• Biochemistry
• Developmental Biology

Background:

• The metabolic enzyme Acetyl-CoA Synthetase 2 (ACSS2) regulates alcohol-related changes.
• Its role in prenatal alcohol exposure is currently unknown.

Purpose of the Study:

• To investigate the role of ACSS2 in mediating prenatal alcohol exposure (PAE) phenotypes.
• To identify the mechanisms by which ACSS2 influences fetal brain development under PAE.

Main Methods:

• Proteomic, genomic, and behavioral analyses in mouse models.
• Investigation of ACSS2 nuclear translocation during development.
• Assessment of histone acetylation and gene expression changes in response to PAE.
• Utilizing genetically engineered mice lacking ACSS2 expression.

Main Results:

• ACSS2 nuclear translocation occurs during specific developmental windows in the mouse brain.
• Alcohol-derived acetate is incorporated into fetal brain histone acetylation in utero.
• ACSS2 deficiency significantly attenuates PAE-induced craniofacial abnormalities, motor deficits, and cognitive impairments.
• Loss of ACSS2 prevents associated chromatin and gene expression alterations in the hippocampus and cerebellum.

Conclusions:

• ACSS2 is a critical mediator of PAE-related phenotypes.
• ACSS2 regulates fetal brain development and associated molecular changes under PAE.
• Targeting ACSS2 may offer therapeutic strategies for PAE interventions.