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 microM N-methyl-D-aspartate (NMDA, % viability: NMDA 45.4+/-2.80, NMDA+ALCAR 90.8+/-11.8; P<0.01) and of 5 microM 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 microM; kainate+ALCAR 8.62+/-1.13 microM; 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.
Bigini
P
P
Laboratory for Receptor Pharmacology, Mario Negri Institute for Pharmacological Research, Via Eritrea, 62, 20157 Milan, Italy. bigini@marionegri.it
Larini
S
S
Pasquali
C
C
Muzio
V
V
Mennini
T
T
D000108:Acetylcarnitine / Q000494:pharmacology*; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy; D000818:Animals; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
D018696:Neuroprotective Agents; D009498:Neurotoxins; D018697:Nootropic Agents; D000108:Acetylcarnitine; D002795:Choline O-Acetyltransferase; D020794:Receptor Protein-Tyrosine Kinases