Acetyl-L-carnitine shows neuroprotective and neurotrophic activity in primary culture of rat embryo motoneurons

We evaluated the role of acetyl-L-carnitine (ALCAR) in protecting primary motoneuron cultures exposed to excitotoxic agents or serum-brain derived neurotrophic factor (BDNF) deprived. To exclude that ALCAR works as a metabolic source, we compared its effects with those Of L-carnitine (L-CAR), that seems to have no neurotrophic effect. A concentration of 10 mM ALCAR, but not L-CAR, significantly reduced the toxic effect of 50 muM N-methyl-D-aspartate (NMDA, % viability: NMDA 45.4 +/- 2.80, NMDA + ALCAR 90.8 +/- 11.8; P < 0.01) and of 5 mu M kainate in cultured motoneurons (% viability:kainate 40.66 +/- 10.73; kainate + ALCAR 63.80 +/- 13.88; P < 0.05). The effect was due to a shift to the right of the dose-response curve for kainate (EC50 for kainate 5.99 +/- 1.012 muM; kainate + ALCAR 8.62 +/- 1.13 muM; P < 0.05). ALCAR, but not L-CAR, significantly protected against BDNF and serum-deprivation reducing the apoptotic cell death (% viability respect to control: without BDNF/serum 61.8 +/- 13.3: without BDNF/serum + ALCAR 111.8 +/- 13.9; P < 0.01). Immunocytochemistry showed an increase in choline acethyltransferase and tyrosine kinaseB receptors in motoneurons treated with ALCAR but not with L-CAR. These results suggest that ALCAR treatment improves the motoneurons activity, acting as a neurotrophic factor. (C) 2002 Published by Elsevier Science Ireland Ltd.