Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.
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.
['Kocsis|Kitti|K|', 'Frank|Rita|R|', 'Szabó|József|J|', 'Knapp|Levente|L|', 'Kis|Zsolt|Z|', 'Farkas|Tamás|T|', 'Vécsei|László|L|', 'Toldi|József|J|']
D000108:Acetylcarnitine D000818:Animals D002545:Brain Ischemia D056547:CA1 Region, Hippocampal D002867:Chromones D004305:Dose-Response Relationship, Drug D004791:Enzyme Inhibitors D019706:Excitatory Postsynaptic Potentials D005947:Glucose D017774:Long-Term Potentiation D008297:Male D009025:Morpholines D018696:Neuroprotective Agents D019869:Phosphatidylinositol 3-Kinases D000081082:Phosphoinositide-3 Kinase Inhibitors D051057:Proto-Oncogene Proteins c-akt D017208:Rats, Wistar D015398:Signal Transduction D046509:Tissue Culture Techniques
acetyl-l-carnitine neuroprotection long-term potentiation PI3K/Akt ischemia oxygen–glucose deprivation