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Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

Molecular Psychiatry volume 5, pages 616–632 (2000)Cite this article

Abstract

Acetyl-L-carnitine (ALCAR) contains carnitine and acetyl moieties, both of which have neurobiological properties. Carnitine is important in the β-oxidation of fatty acids and the acetyl moiety can be used to maintain acetyl-CoA levels. Other reported neurobiological effects of ALCAR include modulation of: (1) brain energy and phospholipid metabolism; (2) cellular macromolecules, including neurotrophic factors and neurohormones; (3) synaptic morphology; and (4) synaptic transmission of multiple neurotransmitters. Potential molecular mechanisms of ALCAR activity include: (1) acetylation of -NH2 and -OH functional groups in amino acids and N terminal amino acids in peptides and proteins resulting in modification of their structure, dynamics, function and turnover; and (2) acting as a molecular chaperone to larger molecules resulting in a change in the structure, molecular dynamics, and function of the larger molecule. ALCAR is reported in double-blind controlled studies to have beneficial effects in major depressive disorders and Alzheimer's disease (AD), both of which are highly prevalent in the geriatric population.

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References

  1. Marquis NR, Fritz IB . The distribution of carnitine, acetylcarnitine, and carnitine acetyltransferase in rat tissues J Biol Chem 1965; 240: 2193–2196

    CAS  PubMed  Google Scholar 

  2. Broquist HP . Carnitine. In: Shils ME, Olson JA, Shike MS (eds) Modern Nutrition Lea & Febiger: Baltimore 1994; pp 459–465

    Google Scholar 

  3. Fritz IB . Action of carnitine on long chain fatty acid oxidation by liver Am J Physiol 1959; 197: 297–304

    CAS  PubMed  Google Scholar 

  4. Fritz IB, Yue KTN . Effects of carnitine on acetyl-CoA oxidation by heart muscle mitochondria Am J Physiol 1964; 206: 531

    CAS  PubMed  Google Scholar 

  5. Bremer J . The metabolism of fatty acid esters of carnitine by mitochondria J Biol Chem 1962; 237: 3628

    CAS  PubMed  Google Scholar 

  6. Nakano N, Fukatsu R, Fujii M, Miyazawa J, Utsumi K, Hayashi S et al. Relationship between SPECT and pathological alterations in Alzheimer's disease—a study of a case with left-hemisphere dominant lesions. (in Japanese) Seishin Shinkeigaku Zasshi – Psychiatria et Neurologia Japonica 1996; 98: 441–459

    CAS  PubMed  Google Scholar 

  7. Miyazawa S, Ozasa H, Furuta S, Osumi T, Hashimoto T, Miura S et al. Biosynthesis and turnover of carnitine acetyltransferase in rat liver J Biochem 1983; 93: 453–459

    CAS  PubMed  Google Scholar 

  8. Bieber LL . Carnitine Annu Rev Biochem 1988; 57: 261–283

    CAS  PubMed  Google Scholar 

  9. Edwards YH, Chase JF, Edwards MR, Tubbs PK . Carnitine acetyltransferase: the question of multiple forms Eur J Biochem 1974; 46: 209–215

    CAS  PubMed  Google Scholar 

  10. Marzo A, Arrigoni Martelli E, Urso R, Rocchetti M, Rizza V, Kelly JG . Metabolism and disposition of intravenously administered acetyl-L-carnitine in healthy volunteers Eur J Clin Pharmacol 1989; 37: 59–63

    CAS  PubMed  Google Scholar 

  11. Parnetti L, Gaiti A, Mecocci P, Cadini D, Senin U . Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type (published erratum appears in Eur J Clin Pharmacol 1993; 44: 604) Eur J Clin Pharmacol 1992; 42: 89–93

    CAS  PubMed  Google Scholar 

  12. Marzo A, Cardace G, Corbelleta C, Bassani E, Morabito E, Arrigoni Martelli E et al. Homeostatic equilibrium of L-carnitine family before and after i.v. administration of propionyl-L-carnitine in humans, dogs and rats Eur J Drug Metab Pharmacokinet 1991; Spec No 3: 357–363

    CAS  PubMed  Google Scholar 

  13. Kuratsune H, Watanabe Y, Yamaguti K, Jacobsson G, Takahashi M, Machii T et al. High uptake of [2-11C]acetyl-L-carnitine into the brain: a PET study Biochem Biophys Res Commun 1997; 231: 488–493

    CAS  PubMed  Google Scholar 

  14. Aureli T, Di Cocco M, Puccetti C, Ricciolini R, Scalibastri M, Miccheli A et al. Acetyl-L- carnitine modulates glucose metabolism and stimulates glycogen synthesis in rat brain Brain Res 1998; 796: 75–81

    CAS  PubMed  Google Scholar 

  15. Capecchi PL, Laghi Pasini F, Quartarolo E, Di Perri T . Carnitines increase plasma levels of adenosine and ATP in humans Vasc Med 1997; 2: 77–81

    CAS  PubMed  Google Scholar 

  16. Rao KV, Mawal YR, Qureshi IA . Progressive decrease of cerebral cytochrome C oxidase activity in sparse-fur mice: role of acetyl-L-carnitine in restoring the ammonia-induced cerebral energy depletion Neurosci Lett 1997; 224: 83–86

    CAS  PubMed  Google Scholar 

  17. Rosenthal RE, Williams R, Bogaert YE, Getson PR, Fiskum G . Prevention of postischemic canine neurological injury through potentiation of brain energy metabolism by acetyl-L-carnitine Stroke 1992; 23: 1312–1318

    CAS  PubMed  Google Scholar 

  18. Jeulin C, Soufir JC, Marson J, Paquignon M, Dacheux JL . Acetylcarnitine and spermatozoa: relationship with epididymal maturation and motility in the boar and man. (In French) Reprod Nutr Dev 1988; 28: 1317–1327

    CAS  PubMed  Google Scholar 

  19. Fredholm BB . Purinoceptors in the nervous system Pharmacol Toxicol 1995; 76: 228–239

    CAS  PubMed  Google Scholar 

  20. Rudolphi KA, Schubert P, Parkinson FE, Fredholm BB . Neuroprotective role of adenosine in cerebral ischaemia Trends Pharmacol Sci 1992; 13: 439–445

    CAS  PubMed  Google Scholar 

  21. Kobayashi S, Zimmermann H, Millhorn DE . Chronic hypoxia enhances adenosine release in rat PC12 cells by altering adenosine metabolism and membrane transport J Neurochem 2000; 74: 621–632

    CAS  PubMed  Google Scholar 

  22. Kobayashi S, Conforti L, Pun RY, Millhorn DE . Adenosine modulates hypoxia-induced responses in rat PC12 cells via the A2A receptor J Physiol 1998; 508: 95–107

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Hoppel C . The physiological role of carnitine. In: Ferrari R, Di Mauro S, Sherwood G (eds) L-Carnitine and Its Role in Medicine: From Function to Therapy Academic Press: New York 1999; pp 5–20

    Google Scholar 

  24. Parvin R, Pande SV . Enhancement of mitochondrial carnitine and carnitine acylcarnitine translocase-mediated transport of fatty acids into liver mitochondria under ketogenic conditions J Biol Chem 1979; 254: 5423–5429

    CAS  PubMed  Google Scholar 

  25. Villa RF, Turpeenoja L, Benzi G, Giuffrida SM . Action of L-acetylcarnitine on age-dependent modifications of mitochondrial membrane proteins from rat cerebellum Neurochem Res 1988; 13: 909–916

    CAS  PubMed  Google Scholar 

  26. Aureli T, Miccheli A, Ricciolini R, Di Cocco ME, Ramacci MT, Angelucci L et al. Aging brain: effect of acetyl-L-carnitine treatment on rat brain energy and phospholipid metabolism. A study by 31P and 1H NMR spectroscopy Brain Res 1990; 526: 108–112

    CAS  PubMed  Google Scholar 

  27. Arienti G, Ramacci MT, Maccari F, Casu A, Corazzi L . Acetyl-L-carnitine influences the fluidity of brain microsomes and of liposomes made of rat brain microsomal lipid extracts Neurochem Res 1992; 17: 671–675

    CAS  PubMed  Google Scholar 

  28. Butterfield DA, Rangachari A . Acetylcarnitine increases membrane cytoskeletal protein–protein interactions Life Sci 1993; 52: 297–303

    CAS  PubMed  Google Scholar 

  29. Arduini A, Rossi M, Mancinelli G, Belfiglio M, Scurti R, Radatti G et al. Effect of L-carnitine and acetyl-L-carnitine on the human erythrocyte membrane stability and deformability Life Sci 1990; 47: 2395–2400

    CAS  PubMed  Google Scholar 

  30. Paradies G, Ruggiero FM, Gadaleta MN, Quagliariello E . The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria Biochim Biophys Acta 1992; 1103: 324–326

    CAS  PubMed  Google Scholar 

  31. Pieklik JR, Guynn RW . Equilibrium constants of the reactions of choline acetyltransferase, carnitine acetyltransferase, and acetylcholinesterase under physiological conditions J Biol Chem 1975; 250: 4445–4450

    CAS  PubMed  Google Scholar 

  32. Guynn RW, Veech RL . The equilibrium constants of the adenosine triphosphate hydrolysis and the adenosine triphosphate-citrate lyase reactions J Biol Chem 1973; 248: 6966–6972

    CAS  PubMed  Google Scholar 

  33. Colucci WJ, Gandour RD . Carnitine acetyltransferase: A review of its biology, enzymology, and bioorganic chemistry Bioorg Chem 1988; 16: 307–334

    CAS  Google Scholar 

  34. McClure RJ, Panchalingam K, Stanley JA, Pettegrew JW . Comparison of the conformation of amyloid beta (1–28) peptide fragment with its Lys28 N-acetyl derivative Soc Neurosci Abstr 1997; 23: 1883–1883

    Google Scholar 

  35. Pisano C, Camerini B, Castorina M, Olivi A, Ambrosini A, Calvani M . Acetyl-L-carnitine is involved in protein acetylation Development, Cell Differentiation and Cancer 1996, 9th International Conference ISD, Pisa, Italy

  36. Swamy-Mruthinti S, Carter AL . Acetyl-L-carnitine decreases glycation of lens proteins: in vitro studies Exp Eye Res 1999; 69: 109–115

    CAS  PubMed  Google Scholar 

  37. Nadler SG, Strobel HW . Role of electrostatic interactions in the reaction of NADPH-cytochrome P-450 reductase with cytochromes P-450 Arch Biochem Biophys 1988; 261: 418–429

    CAS  PubMed  Google Scholar 

  38. Shen S, Strobel HW . Role of lysine and arginine residues of cytochrome P450 in the interaction between cytochrome P4502B1 and NADPH-cytochrome P450 reductase Arch Biochem Biophys 1993; 304: 257–265

    CAS  PubMed  Google Scholar 

  39. Mathews FS, Argos P, Levine M . The structure of b5 at 2.0 Angstrom resolution Cold Spring Harb Symp Quant Biol 1972; 36: 387–395

    CAS  PubMed  Google Scholar 

  40. Angelucci L, Ramacci MT, Taglialatela G, Hulsebosch C, Morgan B, Werrbach-Perez K et al. Nerve growth factor binding in aged rat central nervous system: effect of acetyl-L-carnitine J Neurosci Res 1988; 20: 491–496

    CAS  PubMed  Google Scholar 

  41. De Simone R, Ramacci MT, Aloe L . Effect of acetyl-L-carnitine on forebrain cholinergic neurons of developing rats Int J Dev Neurosci 1991; 9: 39–46

    CAS  PubMed  Google Scholar 

  42. Taglialatela G, Angelucci L, Ramacci MT, Werrbach-Perez K, Jackson GR, Perez-Polo JR . Acetyl-L-carnitine enhances the response of PC12 cells to nerve growth factor Brain Res Dev Brain Res 1991; 59: 221–230

    CAS  PubMed  Google Scholar 

  43. Taglialatela G, Angelucci L, Ramacci MT, Werrbach-Perez K, Jackson GR, Perez-Polo JR . Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine Biochem Pharmacol 1992; 44: 577–585

    CAS  PubMed  Google Scholar 

  44. Taglialatela G, Navarra D, Olivi A, Ramacci MT, Werrbach-Perez K, Perez-Polo JR et al. Neurite outgrowth in PC12 cells stimulated by acetyl-L-carnitine arginine amide Neurochem Res 1995; 20: 1–9

    CAS  PubMed  Google Scholar 

  45. Taglialatela G, Navarra D, Cruciani R, Ramacci MT, Alema GS, Angelucci L . Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats Exp Gerontol 1994; 29: 55–66

    CAS  PubMed  Google Scholar 

  46. Piovesan P, Pacifici L, Taglialatela G, Ramacci MT, Angelucci L . Acetyl-L-carnitine treatment increases choline acetyltransferase activity and NGF levels in the CNS of adult rats following total fimbria-fornix transection Brain Res 1994; 633: 77–82

    CAS  PubMed  Google Scholar 

  47. Taglialatela G, Caprioli A, Giuliani A, Ghirardi O . Spatial memory and NGF levels in aged rats: natural variability and effects of acetyl-L-carnitine treatment Exp Gerontol 1996; 31: 577–587

    CAS  PubMed  Google Scholar 

  48. McDonald NQ, Lapatto R, Murray-Rust J, Gunning J, Wlodawer A, Blundell TL . New protein fold revealed by a 2.3-A resolution structure of nerve growth factor Nature 1991; 354: 411–414

    CAS  PubMed  Google Scholar 

  49. Liu Y, Rosenthal RE, Stark-Reed P, Fiskum G . Inhibition of postcardiac arrest brain protein oxidation by acetyl-L-carnitine Free Radic Biol Med 1993; 15: 667–670

    CAS  PubMed  Google Scholar 

  50. Gorini A, D'Angelo A, Villa RF . Action of L-acetylcarnitine on different cerebral mitochondrial populations from cerebral cortex Neurochem Res 1998; 23: 1485–1491

    CAS  PubMed  Google Scholar 

  51. Gorini A, Ghigini B, Villa RF . Acetylcholinesterase activity of synaptic plasma membranes during ageing: effect of L-acetylcarnitine Dementia 1996; 7: 147–154

    CAS  PubMed  Google Scholar 

  52. Terwel D, Prickaerts J, Meng F, Jolles J . Brain enzyme activities after intracerebroventricular injection of streptozotocin in rats receiving acetyl-L-carnitine Eur J Pharmacol 1995; 287: 65–71

    CAS  PubMed  Google Scholar 

  53. Pascale A, Milano S, Corsico N, Lucchi L, Battaini F, Martelli EA et al. Protein kinase C activation and anti-amnesic effect of acetyl-L-carnitine: in vitro and in vivo studies Eur J Pharmacol 1994; 265: 1–7

    CAS  PubMed  Google Scholar 

  54. Florio T, Meucci O, Grimaldi M, Ventra C, Cocozza E, Avallone A et al. Effect of acetyl-L-carnitine treatment on brain adenylate cyclase activity in young and aged rats Eur Neuropsychopharmacol 1993; 3: 95–101

    CAS  PubMed  Google Scholar 

  55. Villa RF, Gorini A . Action of L-acetylcarnitine on different cerebral mitochondrial populations from hippocampus and striatum during aging Neurochem Res 1991; 16: 1125–1132

    CAS  PubMed  Google Scholar 

  56. Karpusas M, Holland D, Remington SJ . 1.9-Å structures of ternary complexes of citrate synthase with D- and L-malate: mechanistic implications Biochemistry 1991; 30: 6024–6031

    CAS  PubMed  Google Scholar 

  57. Lappalainen P, Watmough NJ, Greenwood C, Saraste M . Electron transfer between cytochrome c and the isolated CuA domain: identification of substrate-binding residues in cytochrome c oxidase Biochemistry 1995; 34: 5824–5830

    CAS  PubMed  Google Scholar 

  58. Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L et al. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein Science 1991; 253: 872–879

    CAS  PubMed  Google Scholar 

  59. Slemmon JR . Sequence analysis of a proteolyzed site in Drosophila choline acetyltransferase J Neurochem 1989; 52: 1898–1904

    CAS  PubMed  Google Scholar 

  60. Sutton RB, Sprang SR . Structure of the protein kinase Cbeta phospholipid-binding C2 domain complexed with Ca2+ Structure 1998; 6: 1395–1405

    CAS  PubMed  Google Scholar 

  61. Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR . Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha. GTPgammaS Science 1997; 278: 1907–1916

    CAS  PubMed  Google Scholar 

  62. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai L-H . Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration Nature 1999; 402: 615–622

    CAS  PubMed  Google Scholar 

  63. Onofrj M, Bodis-Wollner I, Pola P, Calvani M . Central cholinergic effects of levo-acetylcarnitine Drugs Exp Clin Res 1983; 9: 161–169

    CAS  Google Scholar 

  64. Angelucci L, Ramacci MT . Hypothalamo-pituitary-adenocortical function in aging: effects of acetyl–L–carnitine. In: De Simone R, Martelli EA (eds) Stress, Immunity and Ageing—A Role for Acetyl–L–carnitine Excerpta Medica: Amsterdam 1989; pp 109–118

    Google Scholar 

  65. Costa A, Martignoni E, Bono G, Monzani A, Nappi G . Acetyl–L–carnitine, adrenocortical hyperactivity and pathological aging brain. In: De Simone C, Martelli EA (eds) Stress, Immunity and Ageing—A Role for Acetyl-–L–carnitine Excerpta Medica: Amsterdam 1989; pp 119–124

    Google Scholar 

  66. Ghirardi O, Caprioli A, Ramacci MT, Angelucci L . Effect of long-term acetyl-L-carnitine on stress-induced analgesia in the aging rat Exp Gerontol 1994; 29: 569–574

    CAS  PubMed  Google Scholar 

  67. De Simone C, Calvani M, Catania S, Trinchieri V, Di Fabio S, Santini G et al. Acetyl–L–carnitine as a modulator of the neuro-endocrine-immune interaction in HIV + subjects. In: De Simone C, Martelli EA (eds) Stress, Immunity and Ageing—A Role for Acetyl–L–carnitine Excerpta Medica: Amsterdam 1989; pp 125–138

    Google Scholar 

  68. Fraschini F, Esposti D, Demartini G, Scaglione F, Lucini V, Mariani et al. In vivo and in vitro studies on modulation of the pineal endocrine function by L-acetyl-carnitine in the rat Psychoneuroendocrinology 1991; 16: 417–422

    CAS  PubMed  Google Scholar 

  69. Esposti D, Mariani M, Demartini G, Lucini V, Fraschini F, Mancia M . Modulation of melatonin secretion by acetyl-L-carnitine in adult and old rats J Pineal Res 1994; 17: 132–136

    CAS  PubMed  Google Scholar 

  70. Krsmanovic LZ, Virmani MA, Stojilkovic SS, Catt KJ . Stimulation of gonadotropin-releasing hormone secretion by acetyl-L-carnitine in hypothalamic neurons and GT1 neuronal cells Neurosci Lett 1994; 165: 33–36

    CAS  PubMed  Google Scholar 

  71. Bidzinska B, Petraglia F, Angioni S, Genazzani AD, Criscuolo M, Ficarra G et al. Effect of different chronic intermittent stressors and acetyl-L-carnitine on hypothalamic beta-endorphin and GnRH and on plasma testosterone levels in male rats Neuroendocrinology 1993; 57: 985–990

    CAS  PubMed  Google Scholar 

  72. Krsmanovic LZ, Virmani MA, Stojilkovic SS, Catt KJ . Actions of acetyl-L-carnitine on the hypothalamo-pituitary-gonadal system in female rats J Steroid Biochem Mol Biol 1992; 43: 351–358

    CAS  PubMed  Google Scholar 

  73. Kentroti S, Ramacci MT, Vernadakis A . Acetyl-L-carnitine has a neuromodulatory influence on neuronal phenotypes during early embryogenesis in the chick embryo Brain Res Dev Brain Res 1992; 70: 259–266

    CAS  PubMed  Google Scholar 

  74. Pomponi MG, Neri G . Butyrate and acetyl-carnitine inhibit the cytogenetic expression of the fragile X in vitro Am J Med Genet 1994; 51: 447–450

    CAS  PubMed  Google Scholar 

  75. Laschi R, Badiali DG, Bonvicini F, Centurione L . Ultrastructural aspects of aging rat hippocampus after long-term administration of acetyl-L-carnitine Int J Clin Pharmacol Res 1990; 10: 59–63

    CAS  PubMed  Google Scholar 

  76. Bertoni-Freddari C, Fattoretti P, Casoli T, Spagna C, Casell U . Dynamic morphology of the synaptic junctional areas during aging: the effect of chronic acetyl-L-carnitine administration Brain Res 1994; 656: 359–366

    CAS  PubMed  Google Scholar 

  77. Bertoni-Freddari C, Fattoretti P, Caselli U, Paoloni R . Acetylcarnitine modulation of the morphology of rat hippocampal synapses Anal Quant Cytol Histol 1996; 18: 275–278

    CAS  PubMed  Google Scholar 

  78. Curti D, Dagani F, Galmozzi MR, Marzatico F . Effect of aging and acetyl-L-carnitine on energetic and cholinergic metabolism in rat brain regions Mech Ageing Dev 1989; 47: 39–45

    CAS  PubMed  Google Scholar 

  79. Davis S, Markowska AL, Wenk GL, Barnes CA . Acetyl-L-carnitine: behavioral, electrophysiological, and neurochemical effects Neurobiol Aging 1993; 14: 107–115

    CAS  PubMed  Google Scholar 

  80. De Falco FA, D'Angelo E, Grimaldi G, Scafuro F, Sachez F, Caruso G . Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome. (In Italian) Clinica Terapeutica 1994; 144: 123–127

    CAS  Google Scholar 

  81. Ratnakumari L, Qureshi IA, Maysinger D, Butterworth RF . Developmental deficiency of the cholinergic system in congenitally hyperammonemic spf mice: effect of acetyl-L-carnitine J Pharmacol Exp Ther 1995; 274: 437–443

    CAS  PubMed  Google Scholar 

  82. Piovesan P, Quatrini G, Pacifici L, Taglialatela G, Angelucci L . Acetyl-L-carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria-fornix transection Int J Dev Neurosci 1995; 13: 13–19

    CAS  PubMed  Google Scholar 

  83. Prickaerts J, Blokland A, Honig W, Meng F, Jolles J . Spatial discrimination learning and choline acetyltransferase activity in streptozotocin-treated rats: effects of chronic treatment with acetyl-L-carnitine Brain Res 1995; 674: 142–146

    CAS  PubMed  Google Scholar 

  84. Castorina M, Ferraris L . Acetyl-L-carnitine affects aged brain receptorial system in rodents Life Sci 1994; 54: 1205–1214

    CAS  PubMed  Google Scholar 

  85. Castorina M, Ambrosini AM, Giuliani A, Pacifici L, Ramacci MT, Angelucci L . A cluster analysis study of acetyl-L-carnitine effect on NMDA receptors in aging Exp Gerontol 1993; 28: 537–548

    CAS  PubMed  Google Scholar 

  86. Harsing LGJ, Sershen H, Toth E, Hashim A, Ramacci MT, Lajtha A . Acetyl-L-carnitine release, dopamine in rat corpus striatum: an in vivo microdialysis study Eur J Pharmacol 1992; 218: 117–121

    CAS  PubMed  Google Scholar 

  87. Imperato A, Ramacci MT, Angelucci L . Acetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats Neurosci Lett 1989; 107: 251–255

    CAS  PubMed  Google Scholar 

  88. Sershen H, Harsing LJ, Banay-Schwartz M, Hashim A, Ramacci MT, Lajtha A . Effect of acetyl-L-carnitine on the dopaminergic system in aging brain J Neurosci Res 1991; 30: 555–559

    CAS  PubMed  Google Scholar 

  89. Janiri L, Falcone M, Persico A, Tempesta E . Activity of L-carnitine and L-acetylcarnitine on cholinoceptive neocortical neurons of the rat in vivo J Neural Transm 1991; 86: 135–146

    CAS  Google Scholar 

  90. Fariello RG, Ferraro TN, Golden GT, DeMattei M . Systemic acetyl-L-carnitine elevates nigral levels of glutathione and GABA Life Sci 1988; 43: 289–292

    CAS  PubMed  Google Scholar 

  91. Tempesta E, Janiri L, Pirrongelli C . Stereospecific effects of acetylcarnitine on the spontaneous activity of brain-stem neurons and their responses to acetylcholine and serotonin Neuropharmacology 1985; 24: 43–50

    CAS  PubMed  Google Scholar 

  92. Toth E, Harsing LGJ, Sershen H, Ramacci MT, Lajtha A . Effect of acetyl-L-carnitine on extracellular amino acid levels in vivo in rat brain regions Neurochem Res 1993; 18: 573–578

    CAS  PubMed  Google Scholar 

  93. Santarelli M, Granato A, Sbriccoli A, Gobbi G, Janiri L, Minciacchi D . Alterations of the thalamo-cortical system in rats prenatally exposed to ethanol are prevented by concurrent administration of acetyl-L-carnitine Brain Res 1995; 698: 241–247

    CAS  PubMed  Google Scholar 

  94. Steffen V, Santiago M, de la Cruz CP, Revilla E, Machado A, Cano J . Effect of intraventricular injection of 1-methyl-4-phenylpyridinium: protection by acetyl-L-carnitine Hum Exp Toxicol 1995; 14: 865–871

    CAS  PubMed  Google Scholar 

  95. Forloni G, Angeretti N, Smiroldo S . Neuroprotective activity of acetyl-L-carnitine: studies in vitro J Neurosci Res 1994; 37: 92–96

    CAS  PubMed  Google Scholar 

  96. Galli G, Fratelli M . Activation of apoptosis by serum deprivation in a teratocarcinoma cell line: inhibition by L-acetylcarnitine Exp Cell Res 1993; 204: 54–60

    CAS  PubMed  Google Scholar 

  97. Dell'Anna E, Iuvone L, Calzolari S, Geloso MC . Effect of acetyl-L-carnitine on hyperactivity and spatial memory deficits of rats exposed to neonatal anoxia Neurosci Lett 1997; 223: 201–205

    CAS  PubMed  Google Scholar 

  98. Caprioli A, Markowska AL, Olton DS . Acetyl–L–carnitine: chronic treatment improves spatial acquisition in a new environment in aged rats J Gerontol A Biol Sci Med Sci 1995; 50: B232–B236

    CAS  PubMed  Google Scholar 

  99. Spagnoli A, Lucca U, Menasce G, Bandera L, Cizza G, Forloni G et al. Long-term acetyl-L-carnitine treatment in Alzheimer's disease Neurology 1991; 41: 1726–1732

    CAS  PubMed  Google Scholar 

  100. Pettegrew JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ . Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease Neurobiol Aging 1995; 16: 1–4

    CAS  PubMed  Google Scholar 

  101. Thal LJ, Carta A, Clarke WR, Ferris SH, Friedland RP, Petersen RC et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease Neurology 1996; 47: 705–711

    CAS  PubMed  Google Scholar 

  102. Brooks JO, Yesavage JA, Carta A, Bravi D . Acetyl-L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach Int Psychogeriatr 1998; 10: 193–203

    PubMed  Google Scholar 

  103. Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI . A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group JAMA 1994; 271: 985–991

    CAS  PubMed  Google Scholar 

  104. Maltby N, Broe GA, Creasey H, Jorm AF, Christensen H, Brooks WS . Efficacy of tacrine and lecithin in mild to moderate Alzheimer's disease: double blind trial BMJ 1994; 308: 879–883

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M . Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists’ Collaboration JAMA 1998; 280: 1777–1782

    CAS  PubMed  Google Scholar 

  106. Rosler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial BMJ 1999; 318: 633–638

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT . A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group Neurology 1998; 50: 136–145

    CAS  PubMed  Google Scholar 

  108. van Gool WA . Efficacy of donepezil in Alzheimer′s disease: fact or artifact? Neurology 1999; 52: 218–219

    CAS  PubMed  Google Scholar 

  109. Bayer T . Commentary: another piece of the Alzheimer's jigsaw BMJ 1999; 318: 639

    CAS  PubMed  Google Scholar 

  110. Farlow MR, Lahiri DK, Poirier J, Davignon J, Schneider L, Hui SL . Treatment outcome of tacrine therapy depends on apolipoprotein genotype and gender of the subjects with Alzheimer's disease Neurology 1998; 50: 669–677

    CAS  PubMed  Google Scholar 

  111. Ellison DW, Beal MF, Martin JB . Phosphoethanolamine and ethanolamine are decreased in Alzheimer's disease and Huntington's disease Brain Res 1987; 417: 389–392

    CAS  PubMed  Google Scholar 

  112. Miatto O, Gonzalez G, Buonanno F, Growdon JH . In vitro 31P NMR spectroscopy detects altered phospholipid metabolism in Alzheimer's disease Can J Neurol Sci 1986; 13: 535–539

    CAS  PubMed  Google Scholar 

  113. Nitsch RM, Blusztajn JK, Pittas AG, Slack BE, Growdon JH, Wurtman RJ . Evidence for a membrane defect in Alzheimer disease brain Proc Natl Acad Sci USA 1992; 89: 1671–1675

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Pettegrew JW, Kopp SJ, Minshew NJ, Glonek T, Feliksik JM, Tow JP et al. 31P nuclear magnetic resonance studies of phosphoglyceride metabolism in developing and degenerating brain: preliminary observations J Neuropathol Exp Neurol 1987; 46: 419–430

    CAS  PubMed  Google Scholar 

  115. Pettegrew JW, Minshew NJ, Cohen MM, Kopp SJ, Glonek T . P-31 NMR changes in Alzheimer's and Huntington's disease brain Neurology 1984; 34: (Suppl 1) 281–281

    Google Scholar 

  116. Pettegrew JW, Moossy J, Withers G, McKeag D, Panchalingam K . 31P nuclear magnetic resonance study of the brain in Alzheimer's disease J Neuropathol Exp Neurol 1988; 47: 235–248

    CAS  PubMed  Google Scholar 

  117. Pettegrew JW, Panchalingam K, Klunk WE, McClure RJ, Muenz LR . Alterations of cerebral metabolism in probable Alzheimer's disease; a preliminary study Neurobiol Aging 1994; 15: 117–132

    CAS  PubMed  Google Scholar 

  118. Smith CD, Gallenstein LG, Layton WJ, Kryscio RJ, Markesbery WR . 31P magnetic resonance spectroscopy in Alzheimer's and Pick's disease Neurobiol Aging 1993; 14: 85–92

    CAS  PubMed  Google Scholar 

  119. Cuenod C-A, Kaplan DB, Michot J-L, Jehenson P, Leroy-Willig A, Forette F et al. Phospholipid abnormalities in early Alzheimer's disease Arch Neurol 1995; 52: 89–94

    CAS  PubMed  Google Scholar 

  120. Pettegrew JW, Klunk WE, Kanal E, Panchalingam K, McClure RJ . Changes in brain membrane phospholipid and high-energy phosphate metabolism precede dementia Neurobiol Aging 1995; 16: 973–975

    CAS  PubMed  Google Scholar 

  121. Lassmann H, Fischer P, Jellinger K . Synaptic pathology of Alzheimer's disease Ann N Y Acad Sci 1993; 695: 59–64

    CAS  PubMed  Google Scholar 

  122. Liu X, Erikson C, Brun A . Cortical synaptic changes and gliosis in normal aging, Alzheimer's disease and frontal lobe degeneration Dementia 1996; 7: 128–134

    CAS  PubMed  Google Scholar 

  123. Wakabayashi K, Honer WG, Masliah E . Synapse alterations in the hippocampal-entorhinal formation in Alzheimer's disease with and without Lewy body disease Brain Res 1994; 667: 24–32

    CAS  PubMed  Google Scholar 

  124. Yao PJ, Coleman PD . Reduced O-glycosylated clathrin assembly protein AP180: implication for synaptic vesicle recycling dysfunction in Alzheimer's disease Neurosci Lett 1998; 252: 33–36

    CAS  PubMed  Google Scholar 

  125. Davidsson P, Blennow K . Neurochemical dissection of synaptic pathology in Alzheimer's disease Int Psychogeriatr 1998; 10: 11–23

    CAS  PubMed  Google Scholar 

  126. Sunderland T, Molchan SE, Zubenko GS . Biological markers in Alzheimer disease. In: Bloom M, Kupfer DJ (eds) Psychopharmacology: The Fourth Generation of Progress Raven Press: New York 1995; pp 1389–1399

    Google Scholar 

  127. Marin DB, Davis K . Experimental therapeutics. In: Bloom PE, Kupfer DJ (eds) Psychopharmacology: The Fourth Generation of Progress Raven Press: New York 1995; pp 1417–1426

    Google Scholar 

  128. Rapoport SI . Anatomic and functional brain imaging in Alzheimer's disease. In: Bloom PE, Kupfer DJ (eds) Psychopharmacology: The Fourth Generation of Progress Raven Press: New York 1995; pp 1401–1415

    Google Scholar 

  129. Kish SJ . Brain energy metabolizing enzymes in Alzheimer's disease: alpha-ketoglutarate dehydrogenase complex and cytochrome oxidase Ann N Y Acad Sci 1997; 826: 218–228

    CAS  PubMed  Google Scholar 

  130. Rapoport SI, Hatanpaa K, Brady DR, Chandrasekaran K . Brain energy metabolism, cognitive function and down-regulated oxidative phosphorylation in Alzheimer disease Neurodegeneration 1996; 5: 473–476

    CAS  PubMed  Google Scholar 

  131. Chandrasekaran K, Hatanpaa K, Brady DR, Rapoport SI . Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease Exp Neurol 1996; 142: 80–88

    CAS  PubMed  Google Scholar 

  132. Marcus DL, de Leon MJ, Goldman J, Logan J, Christman DR, Wolf AP et al. Altered glucose metabolism in microvessels from patients with Alzheimer's disease Ann Neurol 1989; 26: 91–94

    CAS  PubMed  Google Scholar 

  133. Leonard BE . Action mechanism of antidepressants. In: Honig A, Van Praag HM (eds) Depression: Neurobiological, Psychological and Therapeutic Advances John Wiley & Sons: New York 1997; pp 459–470

    Google Scholar 

  134. Popoli M, Brunello N, Perez J, Racagni G . Second messenger-regulated protein kinases in the brain: their functional role and the action of antidepressant drugs J Neurochem 2000; 74: 21–33

    CAS  PubMed  Google Scholar 

  135. Mallinger AG, Hanin I . Membrane transport processes in affective illness. In: Usdin E, Hanin I (eds) Biological Markers in Psychiatry and Neurology Pergamon Press: New York 1982; pp 137–151

    Google Scholar 

  136. Pettegrew JW, Nichols JS, Minshew NJ, Rush AJ, Stewart RM . Membrane biophysical studies of lymphocytes and erythrocytes in manic-depressive illness J Affect Disord 1982; 4: 237–247

    CAS  PubMed  Google Scholar 

  137. Pettegrew JW, Woessner DE, Minshew NJ . Sodium-23 NMR analysis of human whole blood, erythrocyte and plasma. Chemical shift, spin relaxation and intracellular sodium concentration studies J Magn Reson 1984; 57: 185–196

    CAS  Google Scholar 

  138. Pettegrew JW . Toward a molecular basis for affective disorders. In: Rush A, Altshuler K (eds) Depression—Basic Mechanisms, Diagnosis and Treatment Guilford Press: New York 1986; pp 183–204

    Google Scholar 

  139. Pettegrew JW, Post JFM, Panchalingam K . 7Li study of normal human erythrocytes J Magn Reson 1987; 71: 504–519

    CAS  Google Scholar 

  140. Pettegrew JW, Short JW, Woessner RD, Strychor S, McKeag DW, Armstrong J et al. The effect of lithium on the membrane molecular dynamics of normal human erythrocytes Biol Psychiatry 1987; 22: 857–871

    CAS  PubMed  Google Scholar 

  141. Hibbeln JR, Palmer JW, Davis JM . Are disturbances in lipid-protein interactions by Phospholipase-A2 a predisposing factor in affective illness Biol Psychiatry 1989; 25: 945–961

    CAS  PubMed  Google Scholar 

  142. Pettegrew JW, Minshew NJ, Spiker D, Tretta M, Strychor S, McKeag D et al. Alterations in membrane molecular dynamics in erythrocytes of patients with affective illness Depression 1993; 1: 88–100

    Google Scholar 

  143. Cullis PR, DeKruijff B . Lipid polymorphism and the functional roles of lipids in biological membranes Biochim Biophys Acta 1979; 559: 399–420

    CAS  PubMed  Google Scholar 

  144. Cohen CM . The molecular organization of the red cell membrane skeleton Semin Hematol 1983; 20: 141–158

    CAS  PubMed  Google Scholar 

  145. Benga G, Holmes RP . Interactions between components in biological membranes and their implications for membrane function Prog Biophys Mol Biol 1984; 43: 195–257

    CAS  PubMed  Google Scholar 

  146. Carruthers A, Melchior D . A rapid method of reconstituting human erythrocyte sugar transport proteins Biochemistry 1984; 23: 2712–2718

    CAS  PubMed  Google Scholar 

  147. Connolly T, Carruthers A, Melchior D . Effects of biolayer cholesterol of human erythrocyte hexose transport protein activity in synthetic lecithin bilayers Biochemistry 1985; 24: 2865–2873

    CAS  PubMed  Google Scholar 

  148. Farmer BT, Harmon TM, Butterfield DA . ESR study of the erythrocyte membrane skeletal protein network: influence of the state of aggregation of spectrin on the physical state of membrane proteins, bilayer lipids, and cell surface carbohydrates Biochim Biophys Acta 1985; 821: 420–430

    CAS  PubMed  Google Scholar 

  149. Storch J, Kleinfeld A . The lipid structure of biological membranes Trends Biochem Sci 1985; 10: 418–421

    CAS  Google Scholar 

  150. Carruthers A, Melchior D . How bilayer lipids affect membrane protein activity Trends Biochem Sci 1986; 11: 331–335

    CAS  Google Scholar 

  151. DeLisle RC, Williams JA . Regulation of membrane fusion in secretory exocytosis Annu Rev Physiol 1986; 48: 225–238

    CAS  Google Scholar 

  152. Fong TM, McNamee MG . Correlation between acetylcholine receptor function and structural properties of membranes Biochemistry 1986; 25: 830–840

    CAS  PubMed  Google Scholar 

  153. DeKruijff B . Polymorphic regulation of membrane lipid composition Nature 1987; 329: 587–588

    CAS  Google Scholar 

  154. Hanley M, Jackson T . Return of the magnificient seven Nature 1987; 329: 766–767

    CAS  PubMed  Google Scholar 

  155. Hall Z . Three of a kind: the b-adrenergic receptor, the muscarinic acetylcholine receptor, the rhodopsin Trends Neurosci 1987; 10: 99–101

    CAS  Google Scholar 

  156. Prives H, Fulton A, Penman S, Daniels MP, Christian CN . Interaction of the cytoskeleton framework with acetylcholine receptors on the surface of embryonic muscle cells in culture J Cell Biol 1982; 92: 231–236

    CAS  PubMed  Google Scholar 

  157. Peng H, Froehner S . Association of the postsynaptic 43K protein with newly formed acetylcholine receptor clusters in cultured muscle cells J Cell Biol 1985; 100: 1698–1705

    CAS  PubMed  Google Scholar 

  158. Froehner S . The role of the postsynaptic cytoskeleton in AChR organization Trends Neurosci 1986; 9: 37–41

    CAS  Google Scholar 

  159. Hirokawa N . Quick-freeze, deep-etch visualization of the axonal cytoskeleton Trends Neurosci 1986; 9: 67–71

    Google Scholar 

  160. Peng H, Poo M . Formation and dispersal of acetylcholine receptor clusters in muscle cells Trends Neurosci 1986; 9: 125–129

    CAS  Google Scholar 

  161. Maksymiw R, Sui SF, Gaub H, Sackmann E . Electrostatic coupling of spectrin dimers to phosphatidylserine containing lipid lamellae Biochemistry 1987; 26: 2983–2990

    CAS  PubMed  Google Scholar 

  162. Nelson W, Veshnock PJ . Ankyrin binding to (Na+ + K+) ATPase and implications for the organization of membrane domains in polarized cells Nature 1987; 328: 533–536

    CAS  PubMed  Google Scholar 

  163. Morgan RE, Palinkas LA, Barrett-Connor EL, Wingard DL . Plasma cholesterol and depressive symptoms in older men Lancet 1993; 341: 75–79

    CAS  PubMed  Google Scholar 

  164. Maes M, Smith R, Christophe A, Vandoolaeghe E, Van Gastel A, Neels H et al. Lower serum high-density lipoprotein cholesterol (HDL-C) in major depression and in depressed men with serious suicidal attempts: relationship with immune-inflammatory markers Acta Psychiatr Scand 1997; 95: 212–221

    CAS  PubMed  Google Scholar 

  165. Horsten M, Wamala SP, Vingerhoets A, Orth-Gomer K . Depressive symptoms, social support, and lipid profile in healthy middle-aged women Psychosom Med 1997; 59: 521–528

    CAS  PubMed  Google Scholar 

  166. Brown SL, Salive ME, Harris TB, Simonsick EM, Guralnik JM, Kohout FJ . Low cholesterol concentrations and severe depressive symptoms in elderly people BMJ 1994; 308: 1328–1332

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Olusi SO, Fido AA . Serum lipid concentrations in patients with major depressive disorder Biol Psychiatry 1996; 40: 1128–1131

    CAS  PubMed  Google Scholar 

  168. Maes M, Jacobs MP, Suy E, Vandewoude M, Minner B, Raus J . Effects of dexamethasone on the availability of L-tryptophan and on the insulin and FFA concentrations in unipolar depressed patients Biol Psychiatry 1990; 27: 854–862

    CAS  PubMed  Google Scholar 

  169. Maes M, Smith R, Christophe A, Cosyns P, Desnyder R, Meltzer H . Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids J Affect Disord 1996; 38: 35–46

    CAS  PubMed  Google Scholar 

  170. Peet M, Murphy B, Shay J, Horrobin D . Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients Biol Psychiatry 1998; 43: 315–319

    CAS  PubMed  Google Scholar 

  171. Edwards R, Peet M, Shay J, Horrobin D . Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients J Affect Disord 1998; 48: 149–155

    CAS  PubMed  Google Scholar 

  172. Bohus M, Forstner U, Kiefer C, Gebicke-Harter P, Timmer J, Spraul G et al. Increased sensitivity of the inositol-phospholipid system in neutrophils from patients with acute major depressive episodes Psychiatry Res 1996; 65: 45–51

    CAS  PubMed  Google Scholar 

  173. Smythies JR, Alarcon RD, Morere D, Monti JA, Steele M, Tolbert LC et al. Abnormalities of one-carbon metabolism in psychiatric disorders: study of methionine adenosyltransferase kinetics and lipid composition of erythrocyte membranes Biol Psychiatry 1986; 21: 1391–1398

    CAS  PubMed  Google Scholar 

  174. Tempesta E, Casella L, Pirrongelli C, Janiri L, Calvani M, Ancona L . L-Acetyl carnitine in depressed elderly subjects. A cross-over study vs placebo Drugs Exp Clin Res 1987; 13: 417–423

    CAS  PubMed  Google Scholar 

  175. Villardita C, Smirni P, Vecchio I . Acetyl-L-carnitine in depressed geriatric patients Eur Rev Med Pharm Sci 1983; 6: 1–12

    Google Scholar 

  176. De Simone C, Catania S, Trinchieri V, Tzantzoglou S, Calvani M, Bagiella E . Amelioration of the depression of HIV-infected subjects with L-acetyl carnitine therapy J Drug Dev 1988; 1: 163–166

    Google Scholar 

  177. Nasca D, Zurria G, Aguglia E . Action of acetyl-L-carnitine in association with mianserine on depressed old people New Trends Clin Neuropharmacol 1989; 3: 225–230

    Google Scholar 

  178. Bella R, Bondi R, Raffaele R, Pennisi G . Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders Int J Clin Pharmacol Res 1990; 10: 355–360

    CAS  PubMed  Google Scholar 

  179. Fulgente T, Onofrj M, Del Re ML, Ferracci F, Bazzano S, Ghilardi MF et al. Laevo-acetylcarnitine (NicetileR) treatment of senile depression Clin Tri J 1990; 27: 155–163

    Google Scholar 

  180. Garzya G, Corallo D, Fiore A, Lecciso G, Petrelli G, Zotti C . Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression Drugs Exp Clin Res 1990; 16: 101–106

    CAS  PubMed  Google Scholar 

  181. Gecele M, Francesetti G, Meluzzi A . Acetyl-L-carnitine in aged subjects with major depression: clinical efficacy and effects on the circadian rhythm of cortisol Dementia 1991; 2: 333–337

    Google Scholar 

  182. Reynolds CF, Frank E, Kupfer DJ, Thase ME, Perel JM, Mazumdar S et al. Treatment outcome in recurrent major depression: a post-hoc comparison of elderly (‘young old’) and mid-life patients Am J Psychiatry 1996; 153: 1288–1292

    PubMed  Google Scholar 

  183. Koran LM, Hamilton SH, Hertzman M, Meyers BS, Halaris AE, Tollefson GD et al. Predicting response to fluoxetine in geriatric patients with major depression J Clin Psychopharmacol 1995; 15: 421–427

    CAS  PubMed  Google Scholar 

  184. Levine J, Barak Y, Gonzalves M, Szor H, Elizur A, Kofman O et al. Double-blind, controlled trial of inositol treatment of depression Am J Psychiatry 1995; 152: 792–794

    CAS  PubMed  Google Scholar 

  185. Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial Arch Gen Psychiatry 1999; 56: 407–412

    CAS  PubMed  Google Scholar 

  186. Goodwin FK, Jamison KR . The manic-depressive spectrum Manic-Depressive Illness Oxford University Press: New York 1990; pp 74–85

    Google Scholar 

  187. Hayashi E, Maeda T, Tomita T . The effect of myo-inositol deficiency on lipid metabolism in rats. II. The mechanism of triacylglycerol accumulation in the liver of myo-inositol-deficient rats Biochim Biophys Acta 1974; 360: 146–155

    CAS  PubMed  Google Scholar 

  188. Pettegrew JW, Panchalingam K, Levine J, McClure RJ, Gershon S, Yao JK . Chronic myo–inositol increases rat brain phosphatidylethanolamine plasmalogen Biol Psychiatry 2000; 48: (in press)

  189. Glaser PE, Gross RW . Plasmenylethanolamine facilitates rapid membrane fusion: a stopped-flow kinetic investigation correlating the propensity of a major plasma membrane constituent to adopt an HII phase with its ability to promote membrane fusion Biochemistry 1994; 33: 5805–5812

    CAS  PubMed  Google Scholar 

  190. Nakamura J, Koh N, Sakakibara F, Hamada Y, Hara T, Sasaki H et al. Polyol pathway hyperactivity is closely related to carnitine deficiency in the pathogenesis of diabetic neuropathy of streptozotocin-diabetic rats J Pharmacol Exp Ther 1998; 287: 897–902

    CAS  PubMed  Google Scholar 

  191. Stevens MJ, Lattimer SA, Feldman EL, Helton ED, Millington DS, Sima AA et al. Acetyl-L-carnitine deficiency as a cause of altered nerve myo-inositol content, Na,K- ATPase activity, and motor conduction velocity in the streptozotocin-diabetic rat Metabolism 1996; 45: 865–872

    CAS  PubMed  Google Scholar 

  192. Renshaw PF, Summers JJ, Renshaw CE . Changes in the 31P NMR spectra of cats receiving lithium chloride systemically Biol Psychiatry 1986; 21: 691–694

    Google Scholar 

  193. Joseph N, Renshaw P, Leigh J . Systemic lithium administration alters rat cerebral cortex phospholipids Biol Psychiatry 1987; 22: 540–544

    CAS  PubMed  Google Scholar 

  194. Jope RS . Effects of lithium treatment in vitro and in vivo on acetylcholine metabolism in rat brain J Neurochem 1979; 33: 487–495

    CAS  PubMed  Google Scholar 

  195. Sherman WR, Leavitt AL, Honchar MP, Hallcher LM, Phillips BE . Evidence that lithium alters phosphoinositide metabolism: chronic administration elevates primarily D-myo-inositol-1-phosphate in cerebral cortex of the rat J Neurochem 1981; 36: 1947–1951

    CAS  PubMed  Google Scholar 

  196. Berridge MJ, Downes CP, Hanley MR . Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands Biochem J 1982; 206: 587–595

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Curti D, Dagani F, Galmozzi MR, Marzatico F . Effect of aging and acetyl-L-carnitine on energetic and cholinergic metabolism in rat brain regions Mech Ageing Dev 1989; 47: 39–45

    CAS  PubMed  Google Scholar 

  198. Davis S, Markowska AL, Wenk GL, Barnes CA . Acetyl-L-carnitine: behavioral, electrophysiological, and neurochemical effects Neurobiol Aging 1993; 14: 107–115

    CAS  PubMed  Google Scholar 

  199. Chang MC, Jones CR . Chronic lithium treatment decreases brain phospholipase A2 activity Neurochem Res 1998; 23: 887–892

    CAS  PubMed  Google Scholar 

  200. Friedman E . Lithium's effects on cyclic AMP, membrane transport and cholinergic mechanisms. In: Greshon S, Shopsin B (eds) Lithium: Its Role in Psychiatric Research and Treatments Plenum Press: New York 1973; 203–208

    Google Scholar 

  201. Forn J . Lithium and cyclic AMP. In: Johnson FN (ed) Lithium Research and Therapy Academic Press: New York 1975; pp 485–497

    Google Scholar 

  202. Avissar S, Schreiber G, Danon A, Belmarker RH . Lithium inhibits adrenergic and cholinergic increased in GTP binding in rat cortex Nature 1988; 331: 440–442

    CAS  PubMed  Google Scholar 

  203. Volonter C, Racker E . Lithium stimulation of membrane-bound phospholipase C from C12 cells exposed to nerve growth factor J Neurochem 1988; 51: 1163–1168

    Google Scholar 

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  1. Department of Psychiatry, Neurophysics Laboratory, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    J W Pettegrew, J Levine & R J McClure

  2. Beersheva Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel

    J Levine

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Pettegrew, J., Levine, J. & McClure, R. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Mol Psychiatry 5, 616–632 (2000). https://doi.org/10.1038/sj.mp.4000805

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