AQP4 Attenuated TRAF6/NFκB Activation in Acrylamide-Induced Neurotoxicity

Area of Science:

• Neuroscience
• Toxicology
• Molecular Biology

Background:

• Acrylamide (ACR) is a neurotoxicant found in processed foods and environmental pollutants.
• Mechanisms of ACR-induced neurotoxicity, potentially involving reactive oxygen species (ROS), are not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms of subacute acrylamide toxicity in rats.
• To identify key proteins and pathways involved in ACR-induced neurotoxicity.

Main Methods:

• Subacute toxicity study involving repeated ACR administration (0, 15, 30 mg/kg) to rats for 28 days.
• RNA sequencing of blood and Western blot analysis of brain tissue to assess gene and protein expression.
• In vitro study using Neuro-2a cells with AQP4 transient transfection.

Main Results:

• Rats treated with 30 mg/kg ACR showed hind-limb muscle weakness and increased matrix metalloproteinase (MMP9) expression.
• ACR exposure induced MMP-9 and aquaporin-4 (AQP4) protein expression in rat brain tissues, correlating with neurotoxicity.
• In vitro, AQP4 transfection inhibited MMP-9 and TRAF6 expression, and reduced ACR-induced TRAF6, IκBα, and NFκB activation.

Conclusions:

• ACR-induced neurotoxicity and depressive symptoms are linked to AQP4 downregulation.
• The TRAF6 pathway is implicated in ACR-induced neurotoxicity, with AQP4 playing a regulatory role.