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Oxidized linoleic acid metabolites regulate neuronal morphogenesis in vitro.

Felipe da Costa Souza1, Ana Cristina G Grodzki2, Rhianna K Morgan2

  • 1Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.

Neurochemistry International
|February 9, 2023
PubMed
Summary

Certain oxidized linoleic acid metabolites (OXLAMs) impact infant brain development. This study found specific OXLAMs altered neuron structure, particularly in male rats, highlighting sex-dependent effects on neurodevelopment.

Keywords:
Dendritic arborizationLinoleic acidNeuronal morphogenesisOXLAMsOxylipinsPrimary neuronal cultures

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Biochemistry

Background:

  • Linoleic acid (LA) is crucial for infant brain development.
  • Oxidized LA metabolites (OXLAMs) are hypothesized to mediate LA's effects in the brain.
  • Direct evidence linking OXLAMs to neurodevelopmental processes is limited.

Purpose of the Study:

  • To investigate the effects of specific OXLAMs on key neurodevelopmental processes.
  • To determine if OXLAMs modulate axon outgrowth, dendritic arborization, cell viability, and synaptic connectivity.
  • To explore potential sex-dependent differences in OXLAM responses.

Main Methods:

  • Primary cortical neuron-glia co-cultures from neonatal male and female rats were used.
  • Cultures were exposed to seven different OXLAMs for 48 hours.
  • Axon outgrowth was assessed via Tau-1 immunostaining; dendritic arborization via MAP2B-eGFP expression.

Main Results:

  • 9-hydroxyoctadecadienoic acid (9-HODE) increased axonal outgrowth in male neurons.
  • 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME) decreased axonal outgrowth in male neurons.
  • Dendritic arborization was modulated by 9-HODE, 9-oxo-octadecadienoic acid (9-OxoODE), and 12(13)-epoxyoctadecenoic acid (12(13)-EpOME) in male neurons, and by 12(13)-EpOME in female neurons.
  • Cell viability and synaptic connectivity remained unaffected by OXLAM exposure.

Conclusions:

  • Specific OXLAMs can influence neuronal morphology during early development.
  • The effects of OXLAMs on neuron structure are sex-dependent, with male neurons showing greater susceptibility.
  • These findings contribute to understanding the role of LA metabolites in neurodevelopment.