Neurochemical Research

, Volume 40, Issue 5, pp 875–884 | Cite as

Vitamin C Neuroprotection Against Dose-Dependent Glutamate-Induced Neurodegeneration in the Postnatal Brain

  • Shahid Ali Shah
  • Gwang Ho Yoon
  • Hyun-Ok Kim
  • Myeong Ok Kim
Original Paper


Glutamate-induced excitotoxicity due to over-activation of glutamate receptors and associated energy depletion (phosphorylation and activation of AMPK) results in neuronal cell death in various neurological disorders. Restoration of energy balance during an excitotoxic insult is critical for neuronal survival. Ascorbic acid (vitamin C), an essential nutrient with well-known antioxidant potential, protects the brain from oxidative damage in various models of neurodegeneration. In this study, we reported the therapeutic efficacy of vitamin C in response to glutamate-induced excitation, resulting in energy depletion and apoptosis in the hippocampus of the developing rat brain. A single subcutaneous injection of glutamate at two different concentrations (5 and 10 mg/kg) in postnatal day 7 rat pups increased brain glutamate levels and increased the protein expression of neuronal apoptotic markers. Both doses of glutamate upregulated the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2, cytochrome-c release, caspase-3 activation and the expression of PARP-1. However, co-treatment of vitamin C (250 mg/kg) with glutamate decreased brain glutamate levels and reversed the changes induced by glutamate in the developing hippocampus. Interestingly, only a high dose of glutamate caused the phosphorylation and activation of AMPK and induced neuronal cell death, whereas a low dose of glutamate failed to mediate these effects. Vitamin C supplementation reduced the glutamate-induced phosphorylation of AMPK and attenuated neuronal cell death, as assessed morphologically by Fluoro Jade B in the hippocampal CA1 region of the developing brain. Taken together, our results indicated that glutamate in both concentrations is toxic to the immature rat brain, whereas vitamin C is pharmacologically effective against glutamate-induced neurodegeneration.


Glutamate Vitamin C Excitotoxicity Neuroprotection AMPK 



This study was supported by the Pioneer Research Centre Program of the National Research Foundation of Korea, which is funded by the Ministry of Science, ICT & Future Planning (2012-0009521).

Conflict of interest

It is hereby declared that we have no conflicts of interest in this study.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Shahid Ali Shah
    • 1
  • Gwang Ho Yoon
    • 1
  • Hyun-Ok Kim
    • 2
  • Myeong Ok Kim
    • 1
    • 3
  1. 1.Department of Biology and Applied of Life Science (BK 21), College of Natural SciencesGyeongsang National UniversityJinjuRepublic of Korea
  2. 2.School of MedicineGyeongsang National UniversityJinjuRepublic of Korea
  3. 3.Department of Biology, Neuroscience Pioneer Research Center, College of Natural SciencesGyeongsang National UniversityJinjuRepublic of Korea

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