Tau Phosphorylation and Cleavage in Ethanol-Induced Neurodegeneration in the Developing Mouse Brain
- 5 January 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Neurochemical Research
- Vol. 35 (4), 651-659
- https://doi.org/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
This publication has 42 references indexed in Scilit:
- RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspasesNature, 2009
- Ethanol enhances tau accumulation in neuroblastoma cells that inducibly express tauNeuroscience Letters, 2008
- Lithium blocks ethanol-induced modulation of protein kinases in the developing brainBiochemical and Biophysical Research Communications, 2008
- Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patientsJCI Insight, 2007
- Effects of Gangliosides on Ethanol‐Induced Neurodegeneration in the Developing Mouse BrainAlcohol: Clinical and Experimental Research, 2007
- Caspase-3- and calpain-mediated tau cleavage are differentially prevented by estrogen and testosterone in beta-amyloid-treated hippocampal neuronsNeuroscience, 2007
- Expression of Iba1 protein in microglial cells of zitter mutant ratNeuroscience Letters, 2007
- Lithium protects ethanol-induced neuronal apoptosisBiochemical and Biophysical Research Communications, 2006
- Nicotinamide Protects against Ethanol-Induced Apoptotic Neurodegeneration in the Developing Mouse BrainPLoS Medicine, 2006
- Post-ischemic activation of caspase-3 in the rat hippocampus: evidence of an axonal and dendritic localisationNeurochemistry International, 2003