Signal transduction pathways involved in melatonin-induced neuroprotection after focal cerebral ischemia in mice

Ülkan Kilic, Ertugrul Kilic, Russel J Reiter, Claudio L. Bassetti, Dirk M. Hermann

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Because of its favorable action profile in humans, melatonin is a particularly interesting candidate as a neuroprotectant in acute ischemic stroke. Until now, the signaling mechanisms mediating melatonin's neuroprotective actions remained essentially uninvestigated. Herein, we examined the effects of melatonin, administered either orally for 9 wk as a stroke prophylactic (4 mg/kg/day) or intraperitoneally immediately after reperfusion onset (4 mg/kg), on the activation of signal transduction pathways in mice submitted to 90 min of intraluminal middle cerebral artery occlusion, followed by 24 hr of reperfusion. In these studies, melatonin significantly reduced ischemic infarct size by ∼30-35%, as compared with animals receiving diluent (sham) treatment, independent of whether the indole was administered prior to or after ischemia. Under both conditions, animals receiving melatonin exhibited elevated phosphorylated Akt levels in their brains, as determined by Western blots. Additionally, phosphorylation levels of mitogen-activated protein kinase/extracellular-regulated kinase (ERK)-1/-2 and Jun kinase (JNK)-1/-2 were increased following prophylactic, but not acute, melatonin treatment. Our data suggest a role of phosphatidyl inositol-3 kinase/Akt signaling in acute melatonin-induced neuroprotection, while ERK-1/-2 and/or JNK-1/-2 rather appear to be involved in melatonin's long-term effects.

Original languageEnglish (US)
Pages (from-to)67-71
Number of pages5
JournalJournal of Pineal Research
Volume38
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Melatonin
Brain Ischemia
Signal Transduction
Phosphotransferases
Reperfusion
Stroke
Neuroprotection
Middle Cerebral Artery Infarction
Neuroprotective Agents
Phosphatidylinositols
Mitogen-Activated Protein Kinases
Ischemia
Western Blotting
Placebos
Phosphorylation
Brain

Keywords

  • Ischemic tolerance
  • Mitogen-activated protein kinase
  • Neuroprotection
  • Phosphatidyl inositol-3 kinase/Akt

ASJC Scopus subject areas

  • Endocrinology

Cite this

Signal transduction pathways involved in melatonin-induced neuroprotection after focal cerebral ischemia in mice. / Kilic, Ülkan; Kilic, Ertugrul; Reiter, Russel J; Bassetti, Claudio L.; Hermann, Dirk M.

In: Journal of Pineal Research, Vol. 38, No. 1, 01.2005, p. 67-71.

Research output: Contribution to journalArticle

Kilic, Ülkan ; Kilic, Ertugrul ; Reiter, Russel J ; Bassetti, Claudio L. ; Hermann, Dirk M. / Signal transduction pathways involved in melatonin-induced neuroprotection after focal cerebral ischemia in mice. In: Journal of Pineal Research. 2005 ; Vol. 38, No. 1. pp. 67-71.
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