Maternal high-fat diet leads to persistent synaptic instability in mouse offspring via oxidative stress during...

Area of Science:

• Neuroscience
• Developmental Biology
• Metabolic Disorders

Background:

• Maternal obesity negatively impacts offspring neurodevelopment.
• High-fat diet (HFD) in dams leads to brain lipid peroxidation and behavioral issues in pups.
• The specific synaptic mechanisms underlying maternal HFD-induced neurodevelopmental deficits are not fully understood.

Purpose of the Study:

• To investigate the impact of maternal HFD on dendritic spine and filopodia dynamics and morphology in offspring.
• To determine if synaptic impairments persist into adulthood and are influenced by diet post-weaning.
• To explore the role of oxidative stress and potential therapeutic interventions.

Main Methods:

• In vivo two-photon imaging of cerebral cortex in offspring from HFD-fed dams.
• Assessment of dendritic spine and filopodia dynamics and morphology.
• Evaluation of diet effects during lactation and post-weaning.
• Administration of ascorbic acid (antioxidant) during lactation.

Main Results:

• Offspring from HFD-fed dams exhibited unstable dendritic spines and filopodia.
• Synaptic instability and reduced spine density persisted into adulthood, even on a normal diet.
• Severe dendritic spine disruption was observed in offspring exposed to HFD during both gestation and lactation.
• HFD exposure solely during lactation induced synaptic instability and spine loss.
• Ascorbic acid treatment during lactation mitigated synaptic impairments.

Conclusions:

• Maternal obesity via HFD induces persistent synaptic impairments in offspring, potentially contributing to adult behavioral deficits.
• Oxidative stress from peroxidized lipids during lactation may underlie these synaptic deficits.
• Antioxidant intervention during lactation shows promise in ameliorating HFD-induced synaptic damage.