Neuroprotective activity of acetyl‐L‐carnitine: Studies in vitro

The neuroprotective properties of acetyl‐L‐carnitine (ALCAR) were investigated in primary cell cultures from rat hippocampal formation and cerebral cortex of 17‐day‐old rat embryos. Chronic exposure to ALCAR (10–50 μM), reduced the cell mortality induced by 24 hr fetal calf serum deprivation. Protection was partial when the neuronal cells, chronically treated with ALCAR (50 μM,) were exposed to glutamate (0.25‐1 mM)and kainic acid (250–500 μM) for 24 hr. The neurotoxity induced by N‐methyl‐D‐aspartate (NMDA, 250 μm) was attenuated by the acute co‐exposure with ALCAR (1mM), the chronic treatment with ALCAR (50 μM)significantly reduced the neuronal death induced by NMDA (0.25–1mM) Cell mortality was also investigated in ALCAR‐treated hippocampal cultures chronically treated with β‐amyloid fragment 25–35. ALCAR appeared to have neuroprotective activity. This suggests an explanation of the positive results obtained with ALCAR in the treatment of alzheimer's disease. © 1994 Wiley‐Liss, Inc.

[1]  J. Haxby,et al.  Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer's-type dementia. , 1986, Archives of neurology.

[2]  D. Choi,et al.  Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay , 1987, Journal of Neuroscience Methods.

[3]  V. Felipo,et al.  Ammonium Injection Induces an N‐Methyl‐d‐Aspartate Receptor‐Mediated Proteolysis of the Microtubule‐Associated Protein MAP‐2 , 1993, Journal of neurochemistry.

[4]  F. Amenta,et al.  Acetyl-L-Carnitine in the Rat’s Hippocampus Aging: Morphological, Endocrine and Behavioral Correlates , 1988 .

[5]  D. Kirschner,et al.  Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. , 1990, Science.

[6]  A. Novelli,et al.  Neurotoxicity at the N‐Methyl‐D‐Aspartate Receptor in Energy‐Compromised Neurons An Hypothesis for Cell Death in Aging and Disease , 1989, Annals of the New York Academy of Sciences.

[7]  A. Shetter,et al.  Cortical biopsy in Alzheimer's disease: Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations , 1992 .

[8]  Luciano Angelucci,et al.  Effect of acetyl-l-carnitine chronic treatment on discrimination models in aged rats , 1988, Physiology & Behavior.

[9]  G. Taglialatela,et al.  Acetyl-L-carnitine enhances the response of PC12 cells to nerve growth factor. , 1991, Brain research. Developmental brain research.

[10]  G. Taglialatela,et al.  Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine. , 1992, Biochemical pharmacology.

[11]  J. Penney,et al.  Glutamate dysfunction in Alzheimer's disease: an hypothesis , 1987, Trends in Neurosciences.

[12]  G. Forloni,et al.  Culture of dorsal root ganglion neurons from aged rats: Effects of acetyl-l-carnitine and NGF , 1992, International Journal of Developmental Neuroscience.

[13]  M. Beal,et al.  An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Coyle,et al.  Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea , 1976, Nature.

[15]  C. Filley,et al.  Cytochrome oxidase deficiency in Alzheimer's disease , 1990, Neurology.

[16]  I. Fritz.  CARNITINE AND ITS ROLE IN FATTY ACID METABOLISM. , 1963, Advances in lipid research.

[17]  J. Blass,et al.  An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer's disease brain , 1985, Annals of neurology.

[18]  M. Mattson,et al.  beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  R. Rosenthal,et al.  Prevention of Postischemic Canine Neurological Injury Through Potentiation of Brain Energy Metabolism by Acetyl‐L‐Carnitine , 1992, Stroke.

[20]  R. Albin,et al.  Alternative excitotoxic hypotheses , 1992, Neurology.

[21]  G. Forloni,et al.  Apoptosis mediated neurotoxicity induced by chronic application of beta amyloid fragment 25-35. , 1993, Neuroreport.

[22]  M. Beal,et al.  Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? , 1992, Annals of neurology.

[23]  R. Kalaria,et al.  Carnitine acetyltransferase activity in the human brain and its microvessels is decreased in Alzheimer's disease , 1992, Annals of neurology.

[24]  H. Bachelard,et al.  Effects of N‐Methyl‐d‐Aspartate on [Ca2+]i and the Energy State in the Brain by 19F‐ and 31P‐Nuclear Magnetic Resonance Spectroscopy , 1990, Journal of neurochemistry.

[25]  G. Forloni,et al.  Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1. , 1992, Brain research. Molecular brain research.

[26]  M. Ciman,et al.  Stimulation of oxidation of mitochondrial fatty acids and of acetate by acetylcarnitine. , 1965, The Biochemical journal.

[27]  G. Forloni,et al.  Neurotoxicity of a prion protein fragment , 1993, Nature.

[28]  M. Alberoni,et al.  Long‐term acetyl‐L‐carnitine treatment in Alzheimer's disease , 1991, Neurology.