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Journal of Molecular Neuroscience

, Volume 47, Issue 1, pp 67–75 | Cite as

Protective Function of Nicotinamide Against Ketamine-induced Apoptotic Neurodegeneration in the Infant Rat Brain

  • Najeeb Ullah
  • Ikram Ullah
  • Hae Young Lee
  • Muhammad Imran Naseer
  • Park Moon Seok
  • Jawad Ahmed
  • Myeong Ok KimEmail author
Article

Abstract

During development, anesthetics activate neuroapoptosis and produce damage in the central nervous system that leads to several types of neurological disorders. A single dose of ketamine (40 mg/kg) during synaptogenesis in a 7-day-old rat brain activated the apoptotic cascade and caused extensive neuronal cell death in the forebrain. In this study, we investigated the protective effect of nicotinamide against ketamine-induced apoptotic neurodegeneration. After 4 h, neuronal cell death induced by ketamine was associated with the induction of Bax, release of cytochrome c into the cytosol, and activation of caspase-3. One single dose of 1 mg/g nicotinamide was administered to a developing rat and was found to inhibit ketamine-induced neuroapoptosis by downregulating Bax, inhibiting cytochrome c release from mitochondria into cytosol, and inhibiting the expression of activated caspase-3. TUNEL and immunohistochemical analyses showed that ketamine-induced cell death occurred through apoptosis and that it was inhibited by nicotinamide. Fluoro-Jade-B staining demonstrated an increased number of dead cells in the cortex and thalamus after ketamine treatment; treatment with nicotinamide reduced the number of dead cells in these brain regions. Our findings suggest that nicotinamide attenuated ketamine-induced neuronal cell loss in the developing rat brain and is a promising therapeutic and neuroprotective agent for the treatment of neurodevelopmental disorders.

Keywords

Apoptosis Ketamine Neurodegeneration Nicotinamide Neuroprotection NMDA 

Notes

Acknowledgments

This work was supported by Rural Development Administration (Agenda: PJ007361) and Next-Generation Biogreen 21 program (PJ008075) funded by the Korean government.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Najeeb Ullah
    • 1
    • 2
  • Ikram Ullah
    • 1
  • Hae Young Lee
    • 1
  • Muhammad Imran Naseer
    • 1
  • Park Moon Seok
    • 1
  • Jawad Ahmed
    • 2
  • Myeong Ok Kim
    • 1
    Email author
  1. 1.Department of Biology, College of Natural Sciences (RINS) and Applied Life Science (Brain Korea 21)Gyeongsang National UniversityChinjuRepublic of Korea
  2. 2.Institute of Basic Medical SciencesKhyber Medical UniversityPeshawarPakistan

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