Neonatal treatment with monosodium glutamate lastingly facilitates spreading depression in the rat cortex

Life Sci. 2013 Sep 17;93(9-11):388-92. doi: 10.1016/j.lfs.2013.07.009. Epub 2013 Jul 18.


Aims: Monosodium glutamate (MSG) is a neuroexcitatory amino acid used in human food to enhance flavor. MSG can affect the morphological and electrophysiological organization of the brain. This effect is more severe during brain development. Here, we investigated the electrophysiological and morphological effects of MSG in the developing rat brain by characterizing changes in the excitability-related phenomenon of cortical spreading depression (CSD) and microglial reaction.

Main methods: From postnatal days 1-14, Wistar rat pups received 2 or 4 g/kg MSG (groups MSG-2 and MSG-4, respectively; n=9 in each group), saline (n=10) or no treatment (naïve group; n=5) every other day. At 45-60 days, CSD was recorded on two cortical points for 4h. The CSD parameters velocity, and amplitude and duration of the negative potential change were calculated. Fixative-perfused brain sections were immunolabeled with anti-IBA-1 antibodies to identify and quantify cortical microglia.

Key findings: MSG-4 rats presented significantly higher velocities (4.59 ± 0.34 mm/min) than the controls (saline, 3.84 ± 0.20mm/min; naïve, 3.71 ± 0.8mm/min) and MSG-2 group (3.75 ± 0.10mm/min). The amplitude (8.8 ± 2.2 to 11.2 ± 1.9 mV) and duration (58.2 ± 7.1 to 73.6 ± 6.0s) of the negative slow potential shift was similar in all groups. MSG-treatment dose-dependently increased the microglial immunolabeling.

Significance: The results demonstrate a novel, dose-dependent action of MSG in the developing brain, characterized by acceleration of CSD and significant microglial reaction in the cerebral cortex. The CSD effect indicates that MSG can influence cortical excitability, during brain development, as evaluated by CSD acceleration. Data suggest caution when consuming MSG, especially in developing organisms.

Keywords: Brain development; Brain electrophysiology; Food flavoring agent; Glutamatergic system; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium-Binding Proteins / immunology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / growth & development
  • Cortical Spreading Depression / drug effects*
  • Dose-Response Relationship, Drug
  • Electrophysiological Phenomena / drug effects
  • Food Additives / administration & dosage
  • Food Additives / toxicity*
  • Male
  • Microfilament Proteins / immunology
  • Microglia / drug effects*
  • Microglia / metabolism
  • Rats
  • Rats, Wistar
  • Sodium Glutamate / administration & dosage
  • Sodium Glutamate / toxicity*
  • Time Factors


  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Food Additives
  • Microfilament Proteins
  • Sodium Glutamate