Neurochemical Research

, Volume 35, Issue 4, pp 651–659

Tau Phosphorylation and Cleavage in Ethanol-Induced Neurodegeneration in the Developing Mouse Brain

Authors

    • Laboratory of Neurobehavior GeneticsThe Nathan S. Kline Institute for Psychiatric Research
    • Department of PsychiatryNew York University Langone Medical Center
  • Goutam Chakraborty
    • Laboratory of Neurobehavior GeneticsThe Nathan S. Kline Institute for Psychiatric Research
  • Rui-Fen Mao
    • Laboratory of Neurobehavior GeneticsThe Nathan S. Kline Institute for Psychiatric Research
  • Sun-Mee Paik
    • Laboratory of Neurobehavior GeneticsThe Nathan S. Kline Institute for Psychiatric Research
  • Csaba Vadasz
    • Laboratory of Neurobehavior GeneticsThe Nathan S. Kline Institute for Psychiatric Research
    • Department of PsychiatryNew York University Langone Medical Center
  • Mitsuo Saito
    • Division of Analytical PsychopharmacologyThe Nathan S. Kline Institute for Psychiatric Research
    • Department of PsychiatryNew York University Langone Medical Center
Original Paper

DOI: 10.1007/s11064-009-0116-4

Cite this article as:
Saito, M., Chakraborty, G., Mao, R. et al. Neurochem Res (2010) 35: 651. doi:10.1007/s11064-009-0116-4

Abstract

Previous studies indicated that ethanol-induced neurodegeneration in postnatal day 7 (P7) mice, widely used as a model for the fetal alcohol spectrum disorders, was accompanied by glycogen synthase kinase-3β (GSK-3β) and caspase-3 activation. Presently, we examined whether tau, a microtubule associated protein, is modified by GSK-3β and caspase-3 in ethanol-treated P7 mouse forebrains. We found that ethanol increased phosphorylated tau recognized by the paired helical filament (PHF)-1 antibody and by the antibody against tau phosphorylated at Ser199. Ethanol also generated tau fragments recognized by an antibody against caspase-cleaved tau (C-tau). C-tau was localized in neurons bearing activated caspase-3 and fragmented nuclei. Over time, cell debris and degenerated projections containing C-tau appeared to be engulfed by activated microglia. A caspase-3 inhibitor partially blocked C-tau formation. Lithium, a GSK-3β inhibitor, blocked ethanol-induced caspase-3 activation, phosphorylated tau elevation, C-tau formation, and microglial activation. These results indicate that tau is phosphorylated by GSK-3β and cleaved by caspase-3 during ethanol-induced neurodegeneration in the developing brain.

Keywords

EthanolCaspase-cleaved tauGlycogen synthase kinase-3βNeurodegenerationDeveloping brainMicroglia

Copyright information

© Springer Science+Business Media, LLC 2009