title: Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.
abstract: Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. In previous experiments, ALC pretreatment proved to be effective against global hypoperfusion. In the present study, we investigated whether ALC can be protective in an OGD model. We are not aware of any earlier study in which the long-term potentiation (LTP) function on hippocampal slices was measured after OGD. Therefore, we set out to determine whether an effective ALC concentration has an effect on synaptic plasticity after OGD in the hippocampal CA1 subfield of rats. A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500μM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment.
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary; MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary.
authors.forename: Kitti
authors.initials: K
authors.lastname: Kocsis
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Frank
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Szabó
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Knapp
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Kis
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Farkas
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary; MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary; MTA-SZTE Neuroscience Research Group, University of Szeged, Szeged, Hungary. Electronic address: toldi@bio.u-szeged.hu.
authors.forename: József
authors.initials: J
authors.lastname: Toldi
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000172:deficiency*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D046509:Tissue Culture Techniques
chemical_list: D000108:Acetylcarnitine; D002867:Chromones; D004791:Enzyme Inhibitors; D005947:Glucose; D009025:Morpholines; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: PI3K/Akt; acetyl-l-carnitine; ischemia; long-term potentiation; neuroprotection; oxygen–glucose deprivation