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

Ruscher, Karsten (author): Lund University,Lunds universitet,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine

Fernandes, Eduarda (author)

Capela, João Paulo (author)

Bastos, Maria de Lourdes (author)

Wieloch, Tadeusz (author): Lund University,Lunds universitet,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine

Dirnagl, Ulrich (author)

Meisel, Andreas (author)

Carvalho, Félix (author)

(creator_code:org_t)

Elsevier BV, 2011
2011
English.
In: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 1370, s. 43-52

Related links:: http://www.ncbi.nlm....; show more...; http://dx.doi.org/10...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Ruscher, Karsten; Fernandes, Eduar ...; Capela, João Pau ...; Bastos, Maria de ...; Wieloch, Tadeusz; Dirnagl, Ulrich; show more...; Meisel, Andreas; Carvalho, Félix; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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