PMID- 19694907
OWN - NLM
STAT- MEDLINE
DCOM- 20091022
LR  - 20211020
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 111
IP  - 2
DP  - 2009 Oct
TI  - Essential involvement of the NMDA receptor in ethanol preconditioning-dependent 
      neuroprotection from amyloid-betain vitro.
PG  - 580-8
LID - 10.1111/j.1471-4159.2009.06351.x [doi]
AB  - In several epidemiological studies, moderate ethanol consumption has been 
      associated with reduced risks of cognitive decline or Alzheimer's dementia. Of 
      potential relevance is that brain cultures preconditioned with moderate ethanol 
      concentrations are resistant to neurotoxic Alzheimer's amyloid-beta (Abeta) 
      peptides. Using rat cerebellar mixed cultures we investigated whether certain 
      membrane receptors were early 'sensors' in moderate ethanol preconditioning 
      (MEP). In a 6-day MEP protocol (30 mM ethanol), neuroprotection from Abeta25-35 
      was undiminished by antagonism during the first 3 days of either adenosine A(1) 
      or Galpha(i/o) protein-coupled receptors. However, similar cotreatment with 
      memantine or DL-2-amino-5-phosphono-pentanoic acid (AP-5), antagonists of NMDA 
      receptors (NMDAR), abolished neuroprotection, indicating key early involvement of 
      this ionotropic glutamate receptor. Also in these cultures, directly activating 
      NMDAR using subexcitotoxic NMDA preconditioning prevented Abeta neurotoxicity. By 
      day 2 of MEP, we observed increased levels of NMDAR subunits NR1, NR2B, and NR2C 
      that persisted through day 6. Interestingly, memantine co-exposure blocked 
      elevations in the obligatory NR1 subunit. Furthermore, 2 days of MEP 
      significantly increased two indicators of synaptic NMDAR localization, NR2B 
      phospho-Tyr1472, and post-synaptic density 95 scaffolding protein. The results 
      indicate that ethanol preconditioning-dependent neuroprotection is associated 
      with early increases in NR subunits concomitant with enhancement of synaptic 
      localization and activity of NMDAR.
FAU - Mitchell, Robert M
AU  - Mitchell RM
AD  - Department of Pharmacology, Division of Biochemistry, Loyola University Stritch 
      School of Medicine, Maywood, Illinois 60153, USA.
FAU - Neafsey, Edward J
AU  - Neafsey EJ
FAU - Collins, Michael A
AU  - Collins MA
LA  - eng
GR  - R01 AA013568/AA/NIAAA NIH HHS/United States
GR  - R01 AA013568-04/AA/NIAAA NIH HHS/United States
GR  - T32 AA013527/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090819
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (amyloid beta-protein (25-35))
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Alzheimer Disease/metabolism/pathology/*prevention & control
MH  - Amyloid beta-Peptides/metabolism/*toxicity
MH  - Animals
MH  - Cells, Cultured
MH  - Central Nervous System Depressants/*pharmacology
MH  - Cerebellum/cytology
MH  - Dose-Response Relationship, Drug
MH  - Ethanol/*pharmacology
MH  - In Vitro Techniques
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Peptide Fragments/metabolism/*toxicity
MH  - Phosphotyrosine/metabolism
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Synapses/drug effects/metabolism/pathology
PMC - PMC2908385
MID - NIHMS218808
EDAT- 2009/08/22 09:00
MHDA- 2009/10/23 06:00
PMCR- 2010/10/01
CRDT- 2009/08/22 09:00
PHST- 2009/08/22 09:00 [entrez]
PHST- 2009/08/22 09:00 [pubmed]
PHST- 2009/10/23 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - JNC6351 [pii]
AID - 10.1111/j.1471-4159.2009.06351.x [doi]
PST - ppublish
SO  - J Neurochem. 2009 Oct;111(2):580-8. doi: 10.1111/j.1471-4159.2009.06351.x. Epub 
      2009 Aug 19.