liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Propofol causes neurite retraction in neurons
Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Show others and affiliations
2008 (English)In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 101, no 3, 374-379 p.Article in journal (Refereed) Published
Abstract [en]

Background The mechanism by which anaesthetic agents produce general anaesthesia is not yet fully understood. Retraction of neurites is an important function of individual neurones and neural plexuses during normal and pathological conditions, and it has been shown that such a retraction pathway exists in developing and mature neurones. We hypothesized that propofol decreases neuronal activity by causing retraction of neuronal neurites.

Methods Primary cultures of rat cortical neurones were exposed in concentration– and time–response experiments to 0.02, 0.2, 2, and 20 µM propofol or lipid vehicle. Neurones were pretreated with the GABAA receptor (GABAAR) antagonist, bicuculline, the myosin II ATPase activity inhibitor, blebbistatin, and the F-actin stabilizing agent, phalloidin, followed by administration of propofol (20 µM). Changes in neurite retraction were evaluated using time-lapse light microscopy.

Results Propofol caused a concentration- and time-dependent reversible retraction of cultured cortical neurone neurites. Bicuculline, blebbistatin, and phalloidin completely inhibited propofol-induced neurite retraction. Images of retracted neurites were characterized by a retraction bulb and a thin trailing membrane remnant.

Conclusions Cultured cortical rat neurones retract their neurites after exposure to propofol in a concentration- and time-dependent manner. This retraction is GABAAR mediated, reversible, and dependent on actin and myosin II. Furthermore, the concentrations and times to full retraction and recovery correspond to those observed during propofol anaesthesia.

Place, publisher, year, edition, pages
Oxford, UK: Oxford University Press, 2008. Vol. 101, no 3, 374-379 p.
Keyword [en]
Anaesthetics i.v., propofol; brain, GABA rat; theories of anaesthetic action, cellular mechanisms
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-78010DOI: 10.1093/bja/aen185ISI: 000259093300014OAI: oai:DiVA.org:liu-78010DiVA: diva2:530766
Available from: 2012-06-04 Created: 2012-06-04 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Propofol changes the cytoskeletal function in neurons: An experimental study in cortical cultures
Open this publication in new window or tab >>Propofol changes the cytoskeletal function in neurons: An experimental study in cortical cultures
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Every day, general anaesthetics are given to a large number of patients around the world but the cellular mechanisms of how anaesthetics act are still not clear. General anaesthetics cause the intended unconsciousness, amnesia and immobility in patients, but also side effects such as a decrease in mean arterial pressure and arrhythmia, both of which contribute to complications such as heart damage and stroke. With more knowledge of the mechanism of anaesthetic drugs, these complications could be reduced.

It has been shown that anaesthetics cause a disruption of the thalamocortical connectivity and brain network connectivity. How the network communication is disrupted however is not known. Propofol and thiopental are both intravenous anaesthetic drugs used widely in clinical anaesthesia. They bind to the GABAA receptor and enhance its function.

The cytoskeleton helps the cell to maintain its shape and participate in cellular movement and transport. Cellular transport to and from a neuron’s cell body and periphery is performed by motor proteins that move vesicles, organelles and proteins along cytoskeletal tracks. We have previously shown that propofol causes a reorganisation of the cytoskeleton protein actin in neurons, but we were further interested to study the effects of propofol and thiopental on the cytoskeletal function of cultured cortical rat neurons.

Our results show that propofol and thiopental cause neurite (axon and dendrite) retraction. Propofol’s effects were time- and dose-dependent, and can be reversed when propofol is removed. We were able to inhibit propofolinduced neurite retraction if we stabilised actin by blocking either the motor protein myosin II or the GABAA receptor. We have previously shown that a small GTP-binding protein, RhoA, inhibits propofol-caused actin reorganisation. Propofol-induced neurite retraction was mediated via a downstream effector of RhoA, ROK, which induces phosphorylation of the myosin light chain and increases contractility. Furthermore, we have shown that propofol causes a switch from anterograde to retrograde transport and increases the average velocity of the moving vesicles in neurites. The propofol induced retrograde vesicle transport was GABAA receptor-mediated.

Orexin A is a neuropeptide which regulates the sleep/awake cycle and has also been shown to reduce anaesthesia in animals when given intracerebroventricularly. We found that orexin A reverses propofol and thiopental-induced neurite retraction and actin reorganisation. Moreover, we have shown that the orexin A inhibition of propofol-induced neurite retraction is mediated via the PLD/PKC intracellular signalling pathway. Propofol and thiopental decreased the tyrosine phosphorilation of the intermediate cytoskeletal protein vimentin which is reversed by orexin A.

Taken together, these results suggest that propofol causes a time- and dose-dependent, reversible and GABAAreceptor-mediated neurite retraction in cultured cortical rat neurons. Propofol also causes a switch from anterograde to retrograde vesicle transport in neurites. Orexin A reverses propofol and thiopental-induced neurite retraction and cytoskeletal reorganisation. Orexin A inhibits propofol-induced neurite retraction via the PLD/PKC intracellular signalling pathway.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 64 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1305
Keyword
Propofol, cytoskeleton
National Category
Medical and Health Sciences Basic Medicine Neurosciences
Identifiers
urn:nbn:se:liu:diva-77219 (URN)978-91-7519-910-8 (ISBN)
Public defence
2012-06-08, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-06-04 Created: 2012-05-08 Last updated: 2012-06-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Turina, DeanLoitto, VesaBjörnström, KarinSundqvist, TommyEintrei, Christina

Search in DiVA

By author/editor
Turina, DeanLoitto, VesaBjörnström, KarinSundqvist, TommyEintrei, Christina
By organisation
AnesthesiologyFaculty of Health SciencesDepartment of Anaesthesiology and Surgery UHLMedical Microbiology
In the same journal
British Journal of Anaesthesia
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 170 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf