PMID- 18354027
OWN - NLM
STAT- MEDLINE
DCOM- 20080425
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 28
IP  - 12
DP  - 2008 Mar 19
TI  - Enhanced tau phosphorylation in the hippocampus of mice treated with 
      3,4-methylenedioxymethamphetamine ("Ecstasy").
PG  - 3234-45
LID - 10.1523/JNEUROSCI.0159-08.2008 [doi]
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) ("Ecstasy") produces neurotoxic effects, 
      which result into an impairment of learning and memory and other neurological 
      dysfunctions. We examined whether MDMA induces increases in tau protein 
      phosphorylation, which are typically associated with Alzheimer's disease and 
      other chronic neurodegenerative disorders. We injected mice with MDMA at 
      cumulative doses of 10-50 mg/kg intraperitoneally, which are approximately 
      equivalent to doses generally consumed by humans. MDMA enhanced the formation of 
      reactive oxygen species and induced reactive gliosis in the hippocampus, without 
      histological evidence of neuronal loss. An acute or 6 d treatment with MDMA 
      increased tau protein phosphorylation in the hippocampus, revealed by both 
      anti-phospho(Ser(404))-tau and paired helical filament-1 antibodies. This 
      increase was restricted to the CA2/CA3 subfields and lasted 1 and 7 d after acute 
      and repeated MDMA treatment, respectively. Tau protein was phosphorylated as a 
      result of two nonredundant mechanisms: (1) inhibition of the canonical Wnt 
      (wingless-type MMTV integration site family) pathway, with ensuing activation of 
      glycogen synthase kinase-3beta; and (2) activation of type-5 cyclin-dependent 
      kinase (Cdk5). MDMA induced the expression of the Wnt antagonist, Dickkopf-1, and 
      the expression of the Cdk5-activating protein, p25. In addition, the increase in 
      tau phosphorylation was attenuated by strategies that rescued the Wnt pathway or 
      inhibited Cdk5. Finally, an impairment in hippocampus-dependent spatial learning 
      was induced by doses of MDMA that increased tau phosphorylation, although the 
      impairment outlasted this biochemical event. We conclude that tau 
      hyperphosphorylation in the hippocampus may contribute to the impairment of 
      learning and memory associated with MDMA abuse.
FAU - Busceti, Carla L
AU  - Busceti CL
AD  - Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy.
FAU - Biagioni, Francesca
AU  - Biagioni F
FAU - Riozzi, Barbara
AU  - Riozzi B
FAU - Battaglia, Giuseppe
AU  - Battaglia G
FAU - Storto, Marianna
AU  - Storto M
FAU - Cinque, Carlo
AU  - Cinque C
FAU - Molinaro, Gemma
AU  - Molinaro G
FAU - Gradini, Roberto
AU  - Gradini R
FAU - Caricasole, Andrea
AU  - Caricasole A
FAU - Canudas, Anna Maria
AU  - Canudas AM
FAU - Bruno, Valeria
AU  - Bruno V
FAU - Nicoletti, Ferdinando
AU  - Nicoletti F
FAU - Fornai, Francesco
AU  - Fornai F
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Dkk1 protein, mouse)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hallucinogens)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (tau Proteins)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.22 (Cdk5 protein, mouse)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Cyclin-Dependent Kinase 5/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hallucinogens/*pharmacology
MH  - Hippocampus/*drug effects
MH  - Immunoprecipitation/methods
MH  - Intercellular Signaling Peptides and Proteins/genetics
MH  - Learning/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Wakefulness/drug effects/physiology
MH  - tau Proteins/*metabolism
PMC - PMC6670724
EDAT- 2008/03/21 09:00
MHDA- 2008/04/26 09:00
PMCR- 2008/09/19
CRDT- 2008/03/21 09:00
PHST- 2008/03/21 09:00 [pubmed]
PHST- 2008/04/26 09:00 [medline]
PHST- 2008/03/21 09:00 [entrez]
PHST- 2008/09/19 00:00 [pmc-release]
AID - 28/12/3234 [pii]
AID - 3331700 [pii]
AID - 10.1523/JNEUROSCI.0159-08.2008 [doi]
PST - ppublish
SO  - J Neurosci. 2008 Mar 19;28(12):3234-45. doi: 10.1523/JNEUROSCI.0159-08.2008.