Abstract
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.
Highlights
Glutamate is an excitatory neurotransmitter in the central nervous system [1]
We confirmed the decrease in these protein levels using western blot analysis (Fig. 2). 14–3-3 proteins expression levels are explained as the ratio of intensity of actin
We identified decreases in 14–3-3 family proteins by glutamate exposure in the neonatal cerebral cortex. 14– 3-3 proteins are involved in multiple cellular processes including signal transduction, apoptosis, cell survival, and cell cycle control. 14–3-3 induces anti-apoptotic effects by interacting with pro-apoptotic proteins such as Bcl-2 associated death promoter (Bad), Bax, and apoptosis signal-regulating kinase 1
Summary
Glutamate is an excitatory neurotransmitter in the central nervous system [1] It contributes to various physiological functions including memory and learning, synaptic transmission, and plasticity [2, 3]. Phosphorylated Bcl-2 associated death promoter (Bad) interacts with 14–3-3 and inactivates its pro-apoptotic function [13]. Our previous study demonstrated that glutamate exposure induces neonatal cerebral cortex damage by modulating a variety of proteins [14]. We propose that glutamate exposure causes neuronal cell death by regulating 14–3-3 proteins during brain development. The objective of this study is to investigate the regulation of 14–3-3 family proteins by glutamate exposure in neonatal cerebral cortex. This study investigates the changes in 14–3-3 proteins by glutamate administration in the neonatal cerebral cortex
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