Browse > Article
http://dx.doi.org/10.4062/biomolther.2012.20.2.207

Krill-Derived Phosphatidylserine Improves TMT-Induced Memory Impairment in the Rat  

Shim, Hyun-Soo (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University)
Park, Hyun-Jung (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University)
Ahn, Yong-Ho (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University)
Her, Song (Korea Basic Science Institute Chuncheon Branch)
Han, Jeong-Jun (Glonet BU, Doosan Co.)
Hahm, Dae-Hyun (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University)
Lee, Hye-Jung (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University)
Shim, In-Sop (Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.20, no.2, 2012 , pp. 207-213 More about this Journal
Abstract
The present study examined the effects of krill-derived phosphatidylserine (Krill-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered vehicle (medium-chain triglyceride: MCT) or Krill-PS (50, 100 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of Krill-PS in TMT-induced amnesic rats was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. The rats with TMT injection showed impaired learning and memory of the tasks and treatment with Krill-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the $2^{nd}$ and $4^{th}$ day compared to that of the MCT group (p<0.05). In the retention test, the Krill-PS+MCT groups showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, Krill-PS 50+MCT group significantly alleviated the loss of acetylcholinergic neurons in the hippocampus and medial septum compared to that of the MCT group. Treatment with Krill-PS significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the MCT group. These results suggest that Krill-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.
Keywords
Trimethyltin (TMT); Choline acetyltransferase (ChAT); Acetylcholinesterase (AChE); cAMP responsive element binding protein (CREB); Krill-derived phosphatidylserine (Krill-PS); Learning and memory;
Citations & Related Records

Times Cited By Web Of Science : 1  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Alessandri, B., FitzGerald, R. E., Schaeppi, U., Krinke, G. J. and Classen, W. (1994) The use of an unbaited tunnel maze in neurotoxicology: I. Trimethyltin-induced brain lesions. Neurotoxicology 15, 349-357.
2 Andersson, H., Luthman, J., Lindqvist, E. and Olson, L. (1995) Timecourse of trimethyltin effects on the monoaminergic systems of the rat brain. Neurotoxicology 16, 201-210.
3 Balaban, C. D., O'Callaghan, J. P. and Billingsley, M. L. (1988) Trimethyltin- induced neuronal damage in the rat brain: comparative studies using silver degeneration stains, immunocytochemistry and immunoassay for neuronotypic and gliotypic proteins. Neuroscience 26, 337-361.   DOI   ScienceOn
4 Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi , D., Schutz, G. and Silva, A. J. (1994) Defi cient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 59-68.   DOI   ScienceOn
5 Cannon, R. L., Hoover, D. B., Baisden, R. H. and Woodruff, M. L. (1994a) Effects of trimethyltin (TMT) on choline acetyltransferase activity in the rat hippocampus. Infl uence of dose and time following exposure. Mol. Chem. Neuropathol. 23, 27-45.   DOI   ScienceOn
6 Cannon, R. L., Hoover, D. B., Baisden, R. H. and Woodruff, M. L. (1994b) The effect of time following exposure to trimethyltin (TMT) on cholinergic muscarinic receptor binding in rat hippocampus. Mol. Chem. Neuropathol. 23, 47-62.   DOI   ScienceOn
7 Casamenti, F., Scali, C. and Pepeu, G. (1991) Phosphatidylserine reverses the age-dependent decrease in cortical acetylcholine release: a microdialysis study. Eur. J. Pharmacol. 194, 11-16.   DOI   ScienceOn
8 Cenacchi, T., Bertoldin, T., Farina, C., Fiori, M. G. and Crepaldi, G. (1993) Cognitive decline in the elderly: a double-blind, placebocontrolled multicenter study on effi cacy of phosphatidylserine administration. Aging (Milano) 5, 123-133.
9 Chang, L. W., Tiemeyer, T. M., Wenger, G. R. and McMillan, D. E. (1983) Neuropathology of trimethyltin intoxication. III. Changes in the brain stem neurons. Environ. Res. 30, 399-411.   DOI   ScienceOn
10 Christ, D., Chang, L. W. and McMillan, D. E. (1989) Neurotoxicological effects of trimethyltin on the stellate ganglion. Neurotoxicol. Teratol. 11, 453-460.   DOI   ScienceOn
11 Crook, T., Petrie, W., Wells, C. and Massari, D. C. (1992) Effects of phosphatidylserine in Alzheimer's disease. Psychopharmacol. Bull. 28, 61-66.
12 D'Hooge, R. and De Deyn, P. P. (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res. Brain Res. Rev. 36, 60-90.   DOI   ScienceOn
13 Fortemps, E., Amand, G., Bomboir, A., Lauwerys, R. and Laterre, E. C. (1978) Trimethyltin poisoning. Report of two cases. Int. Arch. Occup. Environ Health 41, 1-6.   DOI   ScienceOn
14 Dyer, R. S. (1982) Physiological methods for assessment of Trimethyltin exposure. Neurobehav. Toxicol. Teratol. 4, 659-664.
15 Earley, B., Burke, M. and Leonard. B. E. (1992) Behavioural, biochemical and histological effects of trimethyltin (TMT) induced brain damage in the rat. Neurochem. Int. 21, 351-366.   DOI   ScienceOn
16 Earley, B., Burke, M., Leonard, B. E., Gouret, C. J. and Junien, J. L. (1990) A comparison of the psychopharmacological profi les of phencyclidine, ketamine and (+) SKF 10,047 in the trimethyltin rat model. Neuropharmacology 29, 695-703.   DOI
17 Freyz L, D. J. and Vincendon C. (1982) Asymmetry of brain microsomal membrances. In Phospholipids in thenervous system (L. Horrocks, Ed.), Vol. 1, pp. 37-47. Raven Press, NewYork.
18 Giacobini, E. (1998) Cholinergic foundations of Alzheimer's disease therapy. J. Physiol. Paris. 92, 283-287.   DOI   ScienceOn
19 Guzowski, J. F. and McGaugh, J. L. (1997) Antisense oligodeoxynucleotide- mediated disruption of hippocampal cAMP response element binding protein levels impairs consolidation of memory for water maze training. Proc. Natl. Acad. Sci. USA. 94, 2693-2698.   DOI   ScienceOn
20 Hagan, J. J., Jansen, J. H. and Broekkamp, C. L. (1988) Selective behavioural impairment after acute intoxication with trimethyltin (TMT) in rats. Neurotoxicology 9, 53-74.
21 Hardingham, G. E. and Bading, H. (2003) The Yin and Yang of NMDA receptor signalling. Trends. Neurosci. 26, 81-89.   DOI   ScienceOn
22 Kataoka-Kato, A., Ukai, M., Sakai, M., Kudo, S. and Kameyama, T. (2005) Enhanced learning of normal adult rodents by repeated oral administration of soybean transphosphatidylated phosphatidylserine. J. Pharmacol. Sci. 98, 307-314.   DOI   ScienceOn
23 Ishida, N., Akaike, M., Tsutsumi, S., Kanai, H., Masui, A., Sadamatsu, M., Kuroda, Y., Watanabe, Y., McEwen, B. S. and Kato, N. (1997) Trimethyltin syndrome as a hippocampal degeneration model: temporal changes and neurochemical features of seizure susceptibility and learning impairment. Neuroscience 81, 1183-1191.   DOI   ScienceOn
24 Izquierdo, I., Izquierdo, L. A., Barros, D. M., Mello e Souza, T., de Souza, M. M., Quevedo, J., Rodrigues, C., Sant'Anna, M. K., Madruga, M. and Medina, J. H. (1998) Differential involvement of cortical receptor mechanisms in working, short-term and long-term memory. Behav. Pharmacol. 9, 421-427.   DOI   ScienceOn
25 Jackson, T. and Ramaswami, M. (2003) Prospects of memory-modifying drugs that target the CREB pathway. Curr. Opin. Drug Discov. Devel. 6, 712-719.
26 Kato-Kataoka, A., Sakai, M., Ebina, R., Nonaka, C., Asano, T. and Miyamori, T. (2010) Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints. J. Clin. Biochem. Nutr. 47, 246-255.   DOI   ScienceOn
27 Kim, J. H., Ha, H. C., Lee, M. S., Kang, J. I., Kim, H. S., Lee, S. Y., Pyun, K. H. and Shim, I. (2007) Effect of Tremella fuciformis on the neurite outgrowth of PC12h cells and the improvement of memory in rats. Biol. Pharm. Bull. 30, 708-714.   DOI   ScienceOn
28 Kogan, J. H., Frankland, P. W., Blendy, J. A., Coblentz, J., Marowitz, Z., Schütz, G. and Silva, A. J. (1997) Spaced training induces normal long-term memory in CREB mutant mice. Curr. Biol. 7, 1-11.
29 Kreyberg, S., Torvik, A., Bjorneboe, A., Wiik-Larsen, W. and Jacobsen, D. (1992) Trimethyltin poisoning: report of a case with postmortem examination. Clin. Neuropathol. 11, 256-259.
30 Lee, B., Sur, B. J., Han, J. J., Shim, I., Her, S., Lee, H. J. and Hahm, D. H. (2010) Krill phosphatidylserine improves learning and memory in Morris water maze in aged rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 34, 1085-1093.   DOI   ScienceOn
31 Lonze, B. E. and Ginty, D. D. (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35, 605- 623.   DOI   ScienceOn
32 Mantamadiotis, T., Lemberger, T., Bleckmann, S. C., Kern, H., Kretz, O., Martin Villalba, A., Tronche, F., Kellendonk, C., Gau, D., Kapfhammer, J., Otto, C., Schmid, W. and Schutz, G. (2002) Disruption of CREB function in brain leads to neurodegeneration. Nat. Genet. 31, 47-54.   DOI   ScienceOn
33 Mizoguchi, K., Yuzurihara, M., Ishige, A., Sasaki, H. and Tabira, T. (2001) Effect of chronic stress on cholinergic transmission in rat hippocampus. Brain Res. 915, 108-111.   DOI   ScienceOn
34 Mizoguchi, K., Yuzurihara, M., Ishige, A., Sasaki, H. and Tabira, T. (2002) Chronic stress impairs rotarod performance in rats: implications for depressive state. Pharmacol. Biochem. Behav. 71, 79-84.   DOI   ScienceOn
35 Murai, S., Saito, H., Masuda, Y., Odashima, J. and Itoh, T. (1995) AF64A disrupts retrieval processes in long-term memory of mice. Neuroreport. 6, 349-352.
36 O'Connell, A., Earley, B. and Leonard, B. E. (1994a) Changes in muscarinic (M1 and M2 subtypes) and phencyclidine receptor density in the rat brain following trimethyltin intoxication. Neurochem. Int. 25, 243-252.   DOI   ScienceOn
37 O'Connell, A., Earley, B. and Leonard, B. E. (1994b) The neuroprotective effect of tacrine on trimethyltin induced memory and muscarinic receptor dysfunction in the rat. Neurochem. Int. 25, 555-566.   DOI   ScienceOn
38 Paxinos, G., Watson, C., Pennisi, M. and Topple, A. (1985) Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight. J. Neurosci. Methods 13, 139- 143.   DOI   ScienceOn
39 Piovesan, P., Quatrini, G., Pacifi ci, L., Taglialatela, G. and Angelucci, L. (1995) Acetyl-L-carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fi mbria-fornix transection. International Journal of Developmental Neuroscience: the Offi cial Journal of the International Society for Developmental Neuroscience 13, 13-19.   DOI   ScienceOn
40 Perry, E. K., Gibson, P. H., Blessed, G., Perry, R. H. and Tomlinson, B. E. (1977) Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. J. Neurol. Sci. 34, 247-265.   DOI   ScienceOn
41 Pope, C. N., Ho, B. T. and Wright, A. A. (1987) Neurochemical and behavioral effects of N-ethyl-acetylcholine aziridinium chloride in mice. Pharmacol. Biochem. Behav. 26, 365-371.   DOI   ScienceOn
42 Porte, Y., Buhot, M. C. and Mons, N. E. (2008) Spatial memory in the Morris water maze and activation of cyclic AMP response elementbinding (CREB) protein within the mouse hippocampus. Learn. Mem. 15, 885-894.   DOI   ScienceOn
43 Prusiner, S. B. (1991) Molecular biology of prion diseases. Science 252, 1515-1522.   DOI
44 Safer, D. J. and Allen, R. P. (1971) The central effects of scopolamine in man. Biol. Psychiatry. 3, 347-355.
45 Sala, C., Rudolph-Correia, S. and Sheng, M. (2000) Developmentally regulated NMDA receptor-dependent dephosphorylation of cAMP response element-binding protein (CREB) in hippocampal neurons. J. Neurosci. 20, 3529-3536.
46 Sun, H., Hu, Y., Zhang, J. M., Li, S. Y. and He, W. (2003) Effects of one Chinese herbs on improving cognitive function and memory of Alzheimer's disease mouse models. Zhongguo Zhong Yao Za Zhi 28, 751-754.
47 Walsh, T. J., Gallagher, M., Bostock, E. and Dyer, R. S. (1982a) Trimethyltin impairs retention of a passive avoidance task. Neurobehav. Toxicol. Teratol. 4, 163-167.
48 Swartzwelder, H. S., Hepler, J., Holahan, W., King, S. E., Leverenz, H. A., Miller, P. A. and Myers, R. D. (1982) Imparied maze performance in the rat caused by trimethyltin treatment: problem-solving defi cits and perseveration. Neurobehav. Toxicol. Teratol. 4, 169- 176.
49 Taubenfeld, S. M., Wiig, K. A., Bear, M. F. and Alberini, C. M. (1999) A molecular correlate of memory and amnesia in the hippocampus. Nat. Neurosci. 2, 309-310.   DOI   ScienceOn
50 Vakhapova, V., Cohen, T., Richter, Y., Herzog, Y. and Korczyn, A. D. (2010) Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial. Dement. Geriatr. Cogn. Disord. 29, 467-474.   DOI   ScienceOn
51 Walsh, T. J., Miller, D. B. and Dyer, R. S. (1982b) Trimethyltin, a selective limbic system neurotoxicant, impairs radial-arm maze performance. Neurobehav. Toxicol. Teratol. 4, 177-183.
52 Wu, X., Glinn, M. A., Ostrowski, N. L., Su, Y., Ni, B., Cole, H. W., Bryant, H. U. and Paul, S. M. (1999) Raloxifene and estradiol benzoate both fully restore hippocampal choline acetyltransferase activity in ovariectomized rats. Brain Res. 847, 98-104.   DOI   ScienceOn