N.N. Klyueva - Ph.D. (Biol.), Research Scientist, Institute of Experimental Medicine (Saint-Petersburg). E-mail: nnklyueva@gmail.com I.N. Abdurasulova - Ph.D. (Biol.), Leading Research Scientist, Institute of Experimental Medicine (Saint-Petersburg). E-mail: i_abdurasulova@mail.ru E.T. Zakharova - Ph.D. (Biol.), Senior Research, Institute of Experimental Medicine (Saint-Petersburg). E-mail:et_zakharova@mail.ru V.N. Mukhin - Ph.D. (Med.), Senior Research Scientist, Institute of Experimental Medicine (Saint-Petersburg). E-mail: valery.mukhin@gmail.com E.V. Ageeva - Ph.D. (Med.), Research Scientist, Institute of Experimental Medicine (Saint-Petersburg). E-mail:elena_ag@inbox.ru N.G. Nikulcheva - Dr.Sc. (Med.), Leading Research Scientist, Institute of Experimental Medicine (Saint-Petersburg). E-mail: nnklyueva@gmail.com

Alzheimer-s disease is a socially significant disorder which affects people of older age group. The disease is manifested not only by deposition of beta-amyloid and hyperphosphorylated tau protein but also by oxidative stress and metabolic disturbances including disturbance of cholesterol metabolism. Intracerebroventricular administration of beta-amyloid fragment 25-35 is an animal model of Alzheimer-s disease. It is used in pharmacological studies to find chemicals which may be used for treatment Alzheimer\'s disease. Lactoferrin (LF) and insulin (INS) have antioxidant properties, act through transcription factors GIF and Nrf2 and could become potential means for treatment of Alzheimer-s disease. The purpose of our study was to investigate spectrum of serum lipids in rats which were administrated with beta-amyloid intracerebroventricularly and treated with lactoferrin and insuline separately and simultaneously. Male Wistar rats were divided into 7 groups. Because of complexity of experimental influences on animals including anesthesia, surgery, intervention in the brain, and the toxic influence of beta-amyloid there were three control groups. They were the group of intact animals (without any influence), the sham operated group (only anesthesia and surgery without brain intervention) and the group of central administration of saline solution. Rats administered with water solution of fragment 25-35 of amyloid-beta peptide were the third group. The experimental groups of rats were treated intranasally with LF (every other day at the dose of 10 mg/kg) or INS (every other day at the dose of 10 EU/ml) or both substances on alternate days. Administration the substances was started 2 hours after administration of beta-amyloid. The presence of amnesia was evaluated by the novel object recognition test, adaptation reaction in the open field test, learning of operant food-getting behavior in the TSE PhenoMaster system. Obtaining blood samples for lipid spectrum investigation was performed at the day 25 since beta-amyloid was administered. Level of choles terol (CH), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-CH) was determined. Atherogenic index, the percentage of high-density lipoprotein cholesterol from total cholesterol, and low-density lipoprotein cholesterol by the Friedewald equation were calculated. Enzymatic technique was used for lipid detection with testing kits by Randox (England). Results. Administration of beta-amyloid led to disorders in cognitive functions in rats, detectable in the all tests. When used separately, LF and INS showed improvement in the analyzed parameters. But when used simultaneously, they do not. There were not significant atherogenic changes in lipid spectrum in response to beta-amyloid administration. But there was tendency to increase in the percentage of blood alpha-cholesterol (p=0.09). At the response to lactoferrin treatment HFL-CH and the percentage of HFL-CH were increased and atherogenic index was decreased. In contrast, the use of insulin resulted in a sharp increase in atherogenic index. In the rats treated with both LF and INS antiatherogenic serum changes were not observed.

 

1. Hardy J., Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer\'s disease // Trends Pharmacol. Sci. 1991. V.12. №10. P. 383-388.
2. Kudinova N.V., Kudinov A.R., Berezov T.T. Bolezn Alcgejjmera: amiloid beta i metabolizm lipidov // Voprosy medicinskojj khimii. 1998. № 1. S. 28-34.
3. Stepanichev M.JU., Zdobnova I.M., Zarubenko I.I., Lazareva N.A., Guljaeva N.V. Issledovanie ehffektov centralnogo vvedenija β-amiloidnogo peptida (25-35): patomorfologicheskie izmenenija v gippokampe i narushenie prostranstvennojj pamjati // ZHurnal vysshejj nervnojj dejatelnosti. 2004. T. 54. № 5. S. 705-711.
4. Gruden M.A., Davidova T.B., Malisauskas M., Sewell R.D., Voskresenskaya N.I., Wilhelm K., Elistratova E.I., Sherst­nev V.V., Morozova-Roche L.A. Differential neuroimmune markers to the onset of Alzheimer\'s disease neurodegeneration and dementia: autoantibodies to Abeta (25-35) oligomers, S100b and neurotransmitters // J. Neuroimmunol. 2007. V. 186. № 1-2. P. 181-192.