Journal of Veterinary Behavior: Clinical Applications and Research
Volume 3, Issue 2 , Pages 41-51 , March 2008

Phosphatidylserine (PS) as a potential nutraceutical for canine brain aging: A review

  • Maria Cristina Osella, DVM, PhD, Dipl. ECVBM-CA

      Affiliations

    • Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Grugliasco, Italy
  • ,
  • Giovanni Re, DVM, PhD, Dipl. ECVPT

      Affiliations

    • Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Grugliasco, Italy
  • ,
  • Paola Badino, MSc, PhD

      Affiliations

    • Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Grugliasco, Italy
  • ,
  • Luciana Bergamasco, DVM, PhD

      Affiliations

    • Department of Veterinary Morphophysiology, University of Turin, Grugliasco, Italy
  • ,
  • Alda Miolo, DVM, PhD, Dipl. ECVBM-CA

      Affiliations

    • CeDIS Innovet, Innovet Italia Srl, Saccolongo (Padua), Italy
    • Corresponding Author InformationAddress reprint requests and correspondence: Alda Miolo, DVM, PhD, Dipl. ECVBM-CA, CeDIS Innovet Italia, Via Einaudi 13, I35030 Saccolongo (Padua) Italy.

References 

  1. Anonymous . Monograph. Phosphatidylserine. Altern. Med. Rev. 1999;4:115–117
  2. AAFP/AAFM. . American Association of Feline Practitioners/Academy of Feline Medicine. Panel Report on Feline Senior Care. J. Feline Med. Surg. 2005;7:3–32
  3. Alves CS, Andreatini R, da Cunha C, Tufik S, Vital MA. Phosphatidylserine reverses reserpine-induced amnesia. Eur. J. Pharmacol. 2000;404:161–167
  4. Amaducci L. Phosphatidylserine in the treatment of Alzheimer's disease: results of a multicenter study. Psychopharmacol. Bull. 1988;24:130–134
  5. Araujo JA, Studzinski CM, Milgram NW. Further evidence for the cholinergic hypothesis of aging and dementia from the canine model of aging. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2005;29:411–422
  6. Araujo JA, Landsberg G, Miolo A. Assessment of the effects of a phosphatidylserine-containing nutraceutical on visuospatial memory of aged dogs: neuropsychological testing. J. Vet. Pharmacol. Ther. 2006;29(suppl 1):205–206
  7. Baudry M, Massicotte G, Hauge S. Phosphatidylserine increases the affinity of the AMPA/quisqualate receptor in rat brain membranes. Behav. Neural. Biol. 1991;55:137–140
  8. Blokland A, Honig W, Brouns F, Jolles J. Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS. Nutrition. 1999;15:778–783
  9. Boothe DM. Nutraceuticals in veterinary medicine. Part I. Definitions and regulations. Compend. Cont. Ed. Pract. Vet. Nov. 1997;1248–1255
  10. Boothe DM. Balancing fact and fiction of novel ingredients: definitions, regulations and evaluation. Vet. Clin. North. Am. Small. Anim. Pract. 2004;34:7–38
  11. Borghese CM, Gómez RA, Ramírez OA. Phosphatidylserine increases hippocampal synaptic efficacy. Brain Res. Bull. 1993;31:697–700
  12. Borras D, Ferrer I, Pumarola M. Age-related changes in the brain of the dog. Vet. Pathol. 1999;36:202–211
  13. Casamenti F, Scali C, Pepeu G. Phosphatidylserine reverses the age-dependent decrease in cortical acetylcholine release: a microdialysis study. Eur. J. Pharmacol. 1991;194:11–16
  14. Cena F, Colangeli R, Fassola F, Furlanello T, Giussani S, Osella MC, et al. Effect of a combination of phosphatidylserine, Ginkgo biloba, vitamin E and pyridoxine on clinical signs of canine brain aging: a pilot multicentric study. In:  Beata C,  Heath S,  Pageat P editor. Behaviour and Internal Medicine. Marseille: ESVCE; 2005;p. 127–135
  15. Cenacchi B, Baggio C, Palin E. Human tolerability of oral phosphatidylserine assessed through laboratory examinations. Clin. Trials J. 1987;24:125–130
  16. Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G. Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging. 1993;5:123–133
  17. Chweh AY, Leslie SW. Phosphatidylserine enhancement of [3H]gamma-aminobutyric acid uptake by rat whole brain synaptosomes. J. Neurochem. 1982;38:691–695
  18. Claro FT, Silva RH, Frussa-Filho R. Bovine brain phosphatidylserine attenuates scopolamine-induced amnesia. Physiol. Behav. 1999;67:551–554
  19. Claro FT, Patti CL, Abilio VC, Frussa-Filho R, Silva RH. Bovine brain phosphatidylserine attenuates scopolamine induced amnesia in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2006;30:881–886
  20. Cohen SA, Müller WE. Age-related alterations of NMDA-receptor properties in the mouse forebrain: partial restoration by chronic phosphatidylserine treatment. Brain Res. 1992;584:174–180
  21. Colangeli R, Fassola F, Furlanello T, Giussani S, Osella MC, Petrantoni G, et al. Riconoscere e monitorare i segni clinici di invecchiamento cerebrale nel cane: una metodologia per il veterinario generalista. Veterinaria. 2005;19:19–23
  22. Colangeli R, Cena F, Fassola F, Furlanello T, Giussani S, Osella MC, et al. Valutazione dell'effetto e della tollerabilità di un nutraceutico neuroprotettivo contenente fosfatidilserina e Ginkgo biloba sui segni clinici di invecchiamento cerebrale nel cane: studio pilota multicentrico. Veterinaria. 2005;4:13–18
  23. Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. Effects of phosphatidylserine in age-associated memory impairment. Neurology. 1991;41:644–649
  24. Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol. Bull. 1992;28:61–66
  25. Delwaide PJ, Gyselynck-Mambourg AM, Hurlet A, Ylieff M. Double-blind randomized controlled study of phosphatidylserine in senile demented patients. Acta Neurol. Scand. 1986;73:136–140
  26. Di Carlo R, Muccioli G, Ghe' C, Bellussi G, Ravetti D, Genazzani E. Phosphatidylserine activity on prolactin brain receptors of aged rabbits. Prog. Neuropsychopharmacol. Biol. Psychiatry. 1988;12:915–926
  27. Dimakopoulos AC, Mayer RJ. Aspects of neurodegeneration in the canine brain. J. Nutr. 2002;132(6 suppl. 2):1579S–1582S
  28. Engel RR, Satzger W, Gunther W, Kathmann N, Bove D, Gerke S, et al. Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Eur. Neuropsychopharmacol. 1992;2:149–155
  29. Folch J. The chemical structure of phosphatidylserine. J. Biol. Chem. 1948;174:439–450
  30. Fortney WD. Geriatrics and aging. In:  Hoskins JD editors. Geriatrics and gerontology of the dog and cat. St. Louis, MO: Elsevier; 2004;p. 1–4
  31. Freund G, Brophy TR, Scott JD. Membrane fluidization increases low-affinity muscarinic receptor binding in brain: changes with aging. Exp. Gerontol. 1986;21:37–44
  32. Fukuoka A, Nakayama H, Doi K. Immunohistochemical detection of beta-amyloid and beta-amyloid precursor protein in the canine brain and non-neuronal epithelial tissues. Amyloid. 2004;11:173–178
  33. Furushiro M, Suzuki S, Shishido Y, Sakai M, Yamatoya H, Kudo S, et al. Effects of oral administration of soybean lecithin transphosphatidylated phosphatidylserine on impaired learning of passive avoidance in mice. Jpn. J. Pharmacol. 1997;75:447–450
  34. Gagne J, Giguere C, Tocco G, Ohayon M, Thompson RF, Baudry M, et al. Effect of phosphatidylserine on the binding properties of glutamate receptors in brain sections from adult and neonatal rats. Brain Res. 1996;740:337–345
  35. Gavrilov LA, Gavrilova NS. Reliability Theory of Aging and Longevity. In:  Masoro EJ,  Austad SN editor. Handbook of the Biology of Aging. 6th ed.. San Diego, CA: Elsevier Academic Press; 2006;p. 3–42
  36. Gelbmann CM, Muller WE. Chronic treatment with phosphatidylserine restores muscarinic cholinergic receptor deficits in the aged mouse brain. Neurobiol. Aging. 1992;13:45–50
  37. Gianotti C, Porta A, De Graan PN, Oestreicher AB, Nunzi MG. B-50/GAP-43 phosphorylation in hippocampal slices from aged rats: effects of phosphatidylserine administration. Neurobiol. Aging. 1993;14:401–406
  38. Head E, Thornton PL, Tong L, Cotman CW. Initiation and propagation of molecular cascades in human brain aging: insight from the canine model to promote successful aging. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2000;4:777–786
  39. Head E, Liu J, Hagen TM, Muggenburg BA, Milgram NW, Ames BN, et al. Oxidative damage increases with age in a canine model of human brain aging. J. Neurochem. 2002;82:375–381
  40. Head E, Torp R. Insights into Abeta and presenilin from a canine model of human brain aging. Neurobiol. Dis. 2002;9:1–10
  41. Head E, Moffat K, Das P, Sarsoza F, Poon WW, Landsberg G, et al. Beta-amyloid deposition and tau phosphorylation in clinically characterized aged cats. Neurobiol. Aging. 2005;26:749–763
  42. Heath SE, Barabas S, Craze PG. Nutritional supplementation in cases of canine cognitive dysfunction—a clinical trial. Appl. Anim. Behav. Sci. 2007;105:284–296
  43. Heywood R, Cozens DD, Richold M. Toxicology of a phosphatidylserine preparation from bovine brain (BC-PS). Clin. Trials J. 1987;24:25–32
  44. Jorissen BL, Brouns F, Van Boxtel MP, Ponds RW, Verhey FR, Jolles J, et al. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment. Nutr. Neurosci. 2001;4:121–134
  45. Jorissen BL, Brouns F, Van Boxtel MP, Riedel WJ. Safety of soy-derived phosphatidylserine in elderly people. Nutr. Neurosci. 2002;5:337–343
  46. Karla, E.K., 2003. Nutraceutical-definition and introduction. AAPS Pharm. Sci. 5, article 25.
  47. Kidd PM. Phosphatidylserine; membrane nutrient for memory. A clinical and mechanistic assessment. Altern. Med. Rev. 1996;1:70–84
  48. Kidd PM. A review of nutrients and botanicals in the integrative management of cognitive dysfunction. Altern. Med. Rev. 1999;4:144–161
  49. Kikkawa U, Kaibuchi K, Takai Y, Nishizuka Y. Phospholipid turnover in signal transduction: protein kinase C and calcium ion as two synergistic mediators. In:  Kuo JF editors. Phospholipids and cellular regulation, Volume II. Boca Raton, FL: CRC Press; 1986;p. 111–126
  50. Landsberg, G.M., Moffat, K., Head, E., 2003. Prevalence, clinical signs, and treatment options for cognitive disfunction in cats. Proceedings 4th International Behav. Meeting, Caloundra, Australia, pp. 77-83.
  51. Landsberg G. Therapeutic agents for the treatment of cognitive dysfunction syndrome in senior dogs. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2005;29:471–479
  52. Landsberg G, Araujo JA. Behavior problems in geriatric pets. Vet. Clin. North Am. Small. Anim. Pract. 2005;35:675–698
  53. Landsberg G. Therapeutic options for cognitive decline in senior pets. J. Am. Anim. Hosp. Assoc. 2006;42:407–413
  54. Landsberg, G.M., Araujo, J.A., 2006. The effects of a proprietary nutraceutical on short-term memory performance on aged dogs. Proceedings 2006 Scientific Congress ACVB/AVSAB, Honolulu. pp. 49–54.
  55. Landsberg, G., 2007. Senior pets: the importance of behavior signs in diagnosis and treatment. Proceedings Michigan Vet. Conference. Lansing, MI.
  56. Landsberg, G., Araujo, J.A., Miolo, A., 2007. The objective assessment of a proprietary neuroprotective nutraceutical on short-term memory of aged dogs. Proceedings 6th International Vet. Behav. Meeting (IVBM).
  57. Loeb C, Marinari UM, Benassi E, Besio G, Cottalasso D, Cupello A, et al. Phosphatidylserine increases in vivo the synaptosomal uptake of exogenous GABA in rats. Exp. Neurol. 1988;99:440–446
  58. Maggioni M, Picotti GB, Bondiolotti GP, Panerai A, Cenacchi T, Nobile P, et al. Effects of phosphatidylserine therapy in geriatric patients with depressive disorders. Acta. Psychiatr. Scand. 1990;81:265–270
  59. Magnusson KR, Scanga C, Wagner AE, Dunlop C. Changes in anesthetic sensitivity and glutamate receptors in the aging canine brain. J. Gerontol. A Biol. Sci. Med. Sci. 55. 2000;B448-454
  60. Milan F, Guidolin D, Polato P. Structural changes of basal forebrain cholinergic neurons in the aged rat. Effect of phosphatidylserine administration. In:  Pepeu G,  Tomlinson B,  Wischik CM editor. New Trends in Aging Research. Padova, Italy: Liviana Press; 1988;p. 221–231
  61. Nerozzi D, Aceti F, Melia E, Magnani A, Marino R, Genovesi G, et al. Phosphatidylserine and memory disorders in the aged. Clin. Ter. 1987;120:399–404
  62. Niewiadomska G, Baksalerska-Pazera M, Gasiorowska A, Mietelska A. Nerve growth factor differentially affects spatial and recognition memory in aged rats. Neurochem. Res. 2006;31:1481–1490
  63. Nolan Y, Martin D, Campbell VA, Lynch MA. Evidence of a protective effect of phosphatidylserine-containing liposomes on lipopolysaccharide-induced impairment of long-term potentiation in the rat hippocampus. J. Neuroimmunol. 2004;151:12–23
  64. Nunzi MG, Milan F, Guidolin D, Toffano G. Dendritic spine loss in hippocampus of aged rats. Effect of brain phosphatidylserine administration. Neurobiol. Aging. 1987;8:501–510
  65. Nunzi MG, Milan F, Guidolin D, Polato P, Toffano G. Effects of phosphatidylserine administration of aged-related structural changes in the rat hippocampus and septal complex. Pharmacopsychiatry. 1989;22(suppl 2):125–128
  66. Osella, M.C., Re, G., Odore, R., Girardi, C., Badino, P., Barbero, R., Bergamasco, L., 2005. Canine cognitive dysfunction: prevalence, clinical signs and treatment with a nutraceutical. Proceedings 5th IVBM meeting, Minneapolis, MN. pp. 14–16.
  67. Osella MC, Re G, Odore R, Girardi C, Badino P, Barbero R, et al. Canine cognitive dysfunction syndrome: prevalence, clinical signs and treatment with a neuroprotective nutraceutical. Appl. Anim. Behav. Sci. 2007;105:297–310
  68. Pageat, P., 1995. Pathologie du comportement du chien, Editions du Point Vétérinaire, Maisons-Alfort Cedex, France.
  69. Pageat P., 1999. Patologia comportamentale del cane. Point Veterinaire Italie, Milan, Italy.
  70. Pageat, P., 2001. Description, clinical and histological validation of the A.R.C.A.D. score (evaluation of age-related cognitive and affective disorders). In: Overall, K.L. (Ed.), Proceedings of the Third International Congress on Veterinary Behavioral Medicine. pp. 83-88.
  71. Palmieri G, Palmieri R, Inzoli MR. Double-blind controlled trial of phosphatidylserine in patients with senile mental deterioration. Clin. Trials. J. 1987;24:73–83
  72. Parent, J., 2002. Dealing with senior moments in your canine patients—neurological problems in older dogs. Proceedings 69th AAHA Annual Meeting. Boston, MA. pp. 435-438.
  73. Pedata F, Giovannelli L, Spignoli G, Giovannini MG, Pepeu G. Phosphatidylserine increases acetylcholine release from cortical slices in aged rats. Neurobiol. Aging. 1985;6:337–339
  74. Pepeu G, Spignoli G, Giovannini MG, Magnani M. The relationship between the behavioral effects of cognition-enhancing drugs and brain acetylcholine. Nootropic drugs and brain acetylcholine. Pharmacopsychiatry. 1989;22(suppl 2):116–119
  75. Pepeu G, Pepeu IM, Amaducci L. A review of phosphatidylserine pharmacological and clinical effects. Is phosphatidylserine a drug for the aging brain?. Pharmacol. Res. 1996;33:73–80
  76. Ransmayr G, Plorer S, Gerstenbrand F, Bauer G. Double-blind placebo-controlled trial of phosphatidylserine in elderly patients with arteriosclerotic encephalopathy. Clin. Trials. J. 1987;24:62–72
  77. Re, G., Miolo, A., Badino, P., 2003. Phosphatidylserine for brain aging in dogs and cats: a pharmacological glance. Proceedings 9th ESVCE Meeting, Salzburg. pp. 53-57.
  78. Rofina JE, Singh K, Skoumalova-Vesela A, van Ederen AM, van Asten AJ, Wilhelm J, et al. Histochemical accumulation of oxidative damage products is associated with Alzheimer-like pathology in the canine. Amyloid. 2004;11:90–100
  79. Sakai M, Yamatoya H, Kudo S. Pharmacological effects of phosphatidylserine enzymatically synthesized from soybean lecithin on brain functions in rodents. J. Nutr. Sci. Vitaminol. 1996;42:47–54
  80. Samson JC. The biological basis of phosphatidylserine pharmacology. Clin. Trials J. 1987;24:1–8
  81. Shinitsky, M., 1999. Kinetics and safety of soy lecithin phosphatidylserine (PS) absorption, Weizmann Institute of Science Rohovot, Israel Study Report, September 1.
  82. Skoumalova A, Rofina J, Schwippelova Z, Gruys E, Wilhelm J. The role of free radicals in canine counterpart of senile dementia of the Alzheimer type. Exp. Gerontol. 2003;38:711–719
  83. Suzuki S, Furushiro M, Takahashi M, Sakai M, Kudo S. Oral administration of soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) reduces ischemic damage in the gerbil hippocampus. Jpn. J. Pharmacol. 1999;81:237–239
  84. Suzuki S, Yamatoya H, Sakai M, Kataoka A, Furushiro M, Kudo S. Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats. J. Nutr. 2001;131:2951–2956
  85. Toffano G, Battistella A, Orlano P. Pharmacokinetics of radiolabeled brain phosphatidylserine. Clin. Trials. J. 1987;24:18–24
  86. Torp R, Head E, Cotman CW. Ultrastructural analyses of beta-amyloid in the aged dog brain: neuronal beta-amyloid is localized to the plasma membrane. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2000;24:801–810
  87. Tsakiris S, Deliconstantinos G. Influence of phosphatidylserine on (Na+ + K+)-stimulated ATPase and acetylcholinesterase activities of dog brain synaptosomal plasma membranes. Biochem. J. 1984;220:301–307
  88. Tsakiris S, Deliconstantinos G. Phosphatidylserine and calmodulin effects on Ca2+-stimulated ATPase activity of dog brain synaptosomal plasma membranes. Int. J. Biochem. 1985;17:1117–1119
  89. Valzelli L, Kozak W, Zanotti A, Toffano G. Activity of phosphatidylserine on memory retrieval and on exploration in mice. Methods. Find. Exp. Clin. Pharmacol. 1987;9:657–660
  90. Vannucchi MG, Casamenti F, Pepeu G. Decrease of acetylcholine release from cortical slices in aged rats: investigations into its reversal by phosphatidylserine. J. Neurochem. 1990;55:819–825
  91. Vannucchi MG, Pepeu G. Effect of phosphatidylserine on acetylcholine release and content in cortical slices from aging rats. Neurobiol. Aging. 1987;8:403–407
  92. Villardita C, Griolis S, Salmeri G. Multicentre clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration. Clin. Trials J. 1987;24:84–93
  93. Weihrauch JL, Son YS. The phospholipid content of foods. J. Am. Oil Chem. Soc. 1983;60:1971–1978
  94. Yamatoya H, Sakai M, Kudo S. The effects of soybean transphosphatidylated phosphatidylserine on cholinergic synaptic functions of mice. Jpn. J. Pharmacol. 2000;84:93–96
  95. Zanotti A, Aporti F, Toffano G, Valzelli L. Effects of phosphatidylserine on avoidance relearning in rats (preliminary observations). Pharmacol. Res. Commun. 1984;16:485–493
  96. Zanotti A, Valzelli L, Toffano G. Reversal of scopolamine-induced amnesia by phosphatidylserine in rats. Psychopharmacology. 1986;90:274–275
  97. Zanotti A, Valzelli L, Toffano G. Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. Psychopharmacology. 1989;99:316–321

PII: S1558-7878(07)00219-5

doi: 10.1016/j.jveb.2007.08.003

Journal of Veterinary Behavior: Clinical Applications and Research
Volume 3, Issue 2 , Pages 41-51 , March 2008