Glutamate is a representative excitatory
neurotransmitter. However, excessive
glutamate exposure causes neuronal
cell damage by generating neuronal excitotoxicity. Excitotoxicity in
neonates caused by
glutamate treatment induces neurological deficits in
adults. The 14–3-3
family proteins are conserved
proteins that are expressed ubiquitously in a variety of
tissues. These
proteins contribute to cellular processes, including
signal transduction,
protein synthesis, and
cell cycle control. We proposed that
glutamate induces neuronal
cell damage by regulating 14–3-3
protein expression in
newborn animals. In this study, we investigated the histopathological changes and 14–3-3
proteins expressions as a result of
glutamate exposure in the neonatal
cerebral cortex.
Rat pups at post-natal day 7 were intraperitoneally administrated with vehicle or
glutamate (10 mg/kg).
Animals were sacrificed 4 h
after treatment, and
brain tissues were fixed for histological study.
Cerebral cortices were isolated and frozen for proteomic study. We observed serious histopathological damages including shrunken
dendrites and atypical
neurons in
glutamate-treated
cerebral cortices. In addition, we identified that 14–3-3
family proteins decreased in
glutamate-exposed
cerebral cortices using a proteomic approach. Moreover,
Western blot analysis provided results that
glutamate treatment in
neonates decreased 14–3-3
family proteins expressions, including the β/α, ζ/δ, γ, ε, τ, and η
isoforms. 14–3-3
proteins are involved in
signal transduction,
metabolism, and anti-apoptotic functions. Thus, our findings suggest that
glutamate induces neonatal neuronal
cell damage by modulating 14–3-3
protein expression.