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.

Age-related defects in short-term plasticity are reversed by acetyl-L-carnitine at the mouse calyx of Held

“…We hypothesized that age might impact efficacy of synaptic transmission at the calyx of Held. Additionally, dietary supplementation with ALCAR, an anti-inflammatory compound that facilitates mitochondrial function, is known to improve synaptic resilience and plasticity (Kocsis et al, 2016). We hypothesized that facilitated short-term plasticity may be in part responsible for ALCAR in hearing improvement (S.…”

“…ALCAR treatment has been shown in multiple systems to improve mitochondrial function in CNS, and improve age-related behavioral deficiencies (Aliev et al., 2009; Ando et al, 2001; Hagen et al, 2002; Liu et al, 2002; Mehrotra et al, 2015; Milgram et al., 2007). In addition, ALCAR acts an acute neuroprotectant against ischemic-like loss of transmission in hippocampal slices (Kocsis et al, 2016). ALCAR treatment has been shown previously to not affect multiple parameters of mitochondrial function and behavior in normal young animals (Aliev et al, 2009; Mehrotra et al, 2015) so was not given to juvenile adults used in this study.…”

The Nutraceutical Value of Carnitine and Its Use in Dietary Supplements

“…The in vitro l-carnitine has been reported to reduce phenylalanine-induced DNA damage [64]. The administration of acetyl-l-carnitine (500 µM) exhibited a neuroprotective role by restoring synaptic plasticity and transmission [65]. In a study by Bavari et al [66], the neuroprotective effect of l-carnitine (5 mM) controlled, within 18 h, caffeine cytotoxicity through the regulation of apoptosis-related caspase-3 activity, reducing the DNA fragmentation, inhibition of reactive oxygen species (ROS) generation, elevation of endogenous anti-oxidant defense systems, and the prevention of lipid oxidation.…”

Inhibition of the Akt/PKB Kinase Increases Nav1.6-Mediated Currents and Neuronal Excitability in CA1 Hippocampal Pyramidal Neurons

“…In addition to the aforementioned regulatory effects of Akt throughout the body, the kinase has further been shown to confer important regulatory effects on several intrinsic neuronal properties in developing and adult neurons. For example, the activation of the AKT/mTOR pathway (active, phosphorylated Akt) is essential for neuronal development, neuronal cell survival [29], neurite outgrowth and branching, axonal formation, cytoskeleton organization [30][31][32][33][34][35][36], formation of synapses [32,37], neuronal plasticity and memory [38][39][40][41], and neurodegeneration [42][43][44][45]. Despite these known regulatory effects of Akt on central nervous system CNS neurons, the ultimate molecular targets that are acted upon by Akt to exert these modulatory effects remain poorly understood.…”