PMID- 31219369
OWN - NLM
STAT- MEDLINE
DCOM- 20200812
LR  - 20200812
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Linking)
VI  - 33
IP  - 9
DP  - 2019 Sep
TI  - Effects of MDMA on neuroplasticity, amyloid burden and phospho-tau expression in 
      APPswe/PS1dE9 mice.
PG  - 1170-1182
LID - 10.1177/0269881119855987 [doi]
AB  - BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is still one of the most 
      consumed drugs by adolescents. Its abuse is related with cognitive impairment, 
      which seems due to maladaptive plasticity and neural stress. In turn, new 
      hypotheses suggest that Alzheimer's disease (AD) may be promoted by neural 
      stressors. AIMS AND METHODS: To test if there is an increase in vulnerability to 
      AD after chronic MDMA consumption, we investigated the effects of this drug on 
      recognition memory and its neurotoxic and neuroplastic effects in a transgenic 
      mouse model of presymptomatic familiar AD (APP/PS1 dE9, Tg). RESULTS: 
      MDMA-treated animals showed recognition memory deficits, regardless of genotype, 
      which were accompanied by changes in plasticity markers. Tg mice showed an 
      impaired expression of Arc compared with wild-type animals, but exposure to MDMA 
      induced an increase in the expression of this factor of the same percentage in 
      both genotypes. However, the expression of c-fos, BDNF and p-CREB was not 
      significantly altered by MDMA treatment in Tg mice. Although Tg mice had higher 
      free choline levels than wild-type mice (about 123%), MDMA did not modify these 
      levels in any case, ruling out any specific effect of this drug on the 
      acetylcholine pathway. MDMA treatment significantly increased the presence of 
      cortical amyloid plaques, as well as Abeta40, Abeta42 and secreted APPbeta levels in Tg 
      mice. These plaques were accompanied by increased tau phosphorylation (S199), 
      which does not seem to occur via the canonic pathway involving AKT, CDK5 or 
      GSK3beta. CONCLUSIONS: The present results support previous evidences that MDMA can 
      contribute to the amyloid cascade.
FAU - Abad, Sonia
AU  - Abad S
AD  - Unitat de Farmacologia I Farmacognosia, Facultat de Farmacia, Institut de 
      Biomedicina IBUB, Universitat de Barcelona, Barcelona, Spain.
FAU - Ramon-Duaso, Carla
AU  - Ramon-Duaso C
AD  - Unitat de Farmacologia I Farmacognosia, Facultat de Farmacia, Institut de 
      Biomedicina IBUB, Universitat de Barcelona, Barcelona, Spain.
FAU - Lopez-Arnau, Raul
AU  - Lopez-Arnau R
AD  - Unitat de Farmacologia I Farmacognosia, Facultat de Farmacia, Institut de 
      Biomedicina IBUB, Universitat de Barcelona, Barcelona, Spain.
FAU - Folch, Jaume
AU  - Folch J
AD  - Unitat de Bioquimica i Biotecnologia, Facultat de Medicina i Ciencies de la 
      Salut, Universitat Rovira i Virgili, Reus, Spain.
AD  - Centros de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas 
      (CIBERNED), Madrid, Spain.
FAU - Pubill, David
AU  - Pubill D
AD  - Unitat de Farmacologia I Farmacognosia, Facultat de Farmacia, Institut de 
      Biomedicina IBUB, Universitat de Barcelona, Barcelona, Spain.
FAU - Camarasa, Jordi
AU  - Camarasa J
AD  - Unitat de Farmacologia I Farmacognosia, Facultat de Farmacia, Institut de 
      Biomedicina IBUB, Universitat de Barcelona, Barcelona, Spain.
FAU - Camins, Antoni
AU  - Camins A
AD  - Unitat de Farmacologia I Farmacognosia, Facultat de Farmacia, Institut de 
      Biomedicina IBUB, Universitat de Barcelona, Barcelona, Spain.
AD  - Centros de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas 
      (CIBERNED), Madrid, Spain.
FAU - Escubedo, Elena
AU  - Escubedo E
AUID- ORCID: 0000-0002-5078-366X
AD  - Unitat de Farmacologia I Farmacognosia, Facultat de Farmacia, Institut de 
      Biomedicina IBUB, Universitat de Barcelona, Barcelona, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190620
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Amyloid beta-Peptides)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Alzheimer Disease/metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Cognitive Dysfunction/chemically induced/metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Male
MH  - Memory Disorders/chemically induced/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neuronal Plasticity/*drug effects
MH  - Phosphorylation/*drug effects
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - MDMA
OT  - amyloid plaques
OT  - memory
OT  - mouse model
EDAT- 2019/06/21 06:00
MHDA- 2020/08/13 06:00
CRDT- 2019/06/21 06:00
PHST- 2019/06/21 06:00 [pubmed]
PHST- 2020/08/13 06:00 [medline]
PHST- 2019/06/21 06:00 [entrez]
AID - 10.1177/0269881119855987 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2019 Sep;33(9):1170-1182. doi: 10.1177/0269881119855987. Epub 
      2019 Jun 20.