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Effect of 3,4-Methylenedioxyamphetamine on Dendritic Spines Dynamics in Rat Neocortical Neurons - Involvement of Heat Shock Protein 27.

Ruscher, Karsten LU ; Fernandes, Eduarda; Capela, João Paulo; Bastos, Maria de Lourdes; Wieloch, Tadeusz LU ; Dirnagl, Ulrich; Meisel, Andreas and Carvalho, Félix (2011) In Brain Research 1370. p.43-52
Abstract
Along with chronic neurotoxic effects, the long-term consumption of amphetamines has been associated to psychiatric symptoms and memory disturbances. Dendritic spine dynamics have been discussed as a possible morphological correlate. However, the underlying mechanisms are still elusive. 3,4-Methylenedioxyamphetamine (MDA), a major drug of abuse and a main metabolite after 3,4-methylenedioxymethamphetamine (MDMA) intake, provokes a loss of dendritic spine like protrusions in primary cultures of rat cortical neurons. 3,4-Methylenedioxyamphetamine also induced a rapid activation of the p38 mitogen activated protein kinase (p38 MAPK) pathway and phosphorylation of heat shock protein 27 (hsp27) indicative for its decreased chaperone activity.... (More)
Along with chronic neurotoxic effects, the long-term consumption of amphetamines has been associated to psychiatric symptoms and memory disturbances. Dendritic spine dynamics have been discussed as a possible morphological correlate. However, the underlying mechanisms are still elusive. 3,4-Methylenedioxyamphetamine (MDA), a major drug of abuse and a main metabolite after 3,4-methylenedioxymethamphetamine (MDMA) intake, provokes a loss of dendritic spine like protrusions in primary cultures of rat cortical neurons. 3,4-Methylenedioxyamphetamine also induced a rapid activation of the p38 mitogen activated protein kinase (p38 MAPK) pathway and phosphorylation of heat shock protein 27 (hsp27) indicative for its decreased chaperone activity. Concurrent pharmacological inhibition of the p38 MAPK by SB203580 abolished hsp27 phosphorylation and diminished the loss of dendritic spine-like protrusions. Moreover, upon MDA treatment dendritic spine-like protrusions were stabilized in neurons constitutively expressing hsp27. In parallel experiments we observed a robust activation of the heat shock transcription factor 1 (HSF-1) and a subsequent increase of hsp27 and hsp70. The regulation of small heat shock proteins corroborates the existence of a neuronal stress response after MDA treatment. Pharmacological targeting of small heat shock protein phosphorylation may provide a new strategy to preserve spine integrity after amphetamine exposure. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Dendritic spine, 3, 4-Methylenedioxyamphetamine, Heat shock protein 27, Heat shock transcription factor 1, Neuron, p38 mitogen activated, protein kinase
in
Brain Research
volume
1370
pages
43 - 52
publisher
Elsevier
external identifiers
  • wos:000287065900004
  • pmid:21075084
  • scopus:78651363713
ISSN
1872-6240
DOI
10.1016/j.brainres.2010.11.022
language
English
LU publication?
yes
id
40a3b032-4c72-431a-9b6a-174c8e6c0c4b (old id 1732029)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21075084?dopt=Abstract
date added to LUP
2010-12-01 11:58:49
date last changed
2017-01-01 03:13:54
@article{40a3b032-4c72-431a-9b6a-174c8e6c0c4b,
  abstract     = {Along with chronic neurotoxic effects, the long-term consumption of amphetamines has been associated to psychiatric symptoms and memory disturbances. Dendritic spine dynamics have been discussed as a possible morphological correlate. However, the underlying mechanisms are still elusive. 3,4-Methylenedioxyamphetamine (MDA), a major drug of abuse and a main metabolite after 3,4-methylenedioxymethamphetamine (MDMA) intake, provokes a loss of dendritic spine like protrusions in primary cultures of rat cortical neurons. 3,4-Methylenedioxyamphetamine also induced a rapid activation of the p38 mitogen activated protein kinase (p38 MAPK) pathway and phosphorylation of heat shock protein 27 (hsp27) indicative for its decreased chaperone activity. Concurrent pharmacological inhibition of the p38 MAPK by SB203580 abolished hsp27 phosphorylation and diminished the loss of dendritic spine-like protrusions. Moreover, upon MDA treatment dendritic spine-like protrusions were stabilized in neurons constitutively expressing hsp27. In parallel experiments we observed a robust activation of the heat shock transcription factor 1 (HSF-1) and a subsequent increase of hsp27 and hsp70. The regulation of small heat shock proteins corroborates the existence of a neuronal stress response after MDA treatment. Pharmacological targeting of small heat shock protein phosphorylation may provide a new strategy to preserve spine integrity after amphetamine exposure.},
  author       = {Ruscher, Karsten and Fernandes, Eduarda and Capela, João Paulo and Bastos, Maria de Lourdes and Wieloch, Tadeusz and Dirnagl, Ulrich and Meisel, Andreas and Carvalho, Félix},
  issn         = {1872-6240},
  keyword      = {Dendritic spine,3,4-Methylenedioxyamphetamine,Heat shock protein 27,Heat shock transcription factor 1,Neuron,p38 mitogen activated,protein kinase},
  language     = {eng},
  pages        = {43--52},
  publisher    = {Elsevier},
  series       = {Brain Research},
  title        = {Effect of 3,4-Methylenedioxyamphetamine on Dendritic Spines Dynamics in Rat Neocortical Neurons - Involvement of Heat Shock Protein 27.},
  url          = {http://dx.doi.org/10.1016/j.brainres.2010.11.022},
  volume       = {1370},
  year         = {2011},
}