9th multidisciplinary international

Conference of Biological Psychiatry

«Stress and Behavior»

Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005. Editor: Allan V. Kalueff, PhD

CONFERENCE PLENARY LECTURES

NEUROIMMUNOLOGICAL FEATURES IN ANIMAL MODEL OF ALZHEIMER'S DISEASE

M.I. Aghajanov, H.G. Vahradyan, A.A. Galoyan

Yerevan State Medical University, Institute of Biochemistry NAS RA, Armenia

A new family of peptide neurohormones considered as immunomodulators was discovered by Galoyan and coworkers. They are produced by magnocellular nuclei of hypothalamus, and are isolated from neurosecretory granules of the bovine neurohypophisis. One of those, proline rich polypeptide (PRP), containing 15 amino acid residues, possesses strong antimicrobial, immunomodulating, as well as neuroprotective properties. The obtained data provide evidence to consider PRP as an efficient remedy against neurodegenerative diseases, particularly Alzheimer's disease (AD). The aim of this work was to investigate the protective and curative action of PRP on the model of aluminum neurotoxicosis, where the neurodegenerative disorders are identical to AD. In the blood serum and internal organs of model mice it was studied the content of interleukines (IL-1, IL-2, IL-6) prolactin and insulin-like growth factor-1 (IGF-1). By electron microscopy study of rat hippocampus and other tissues we have succeeded to visualize the epithelioprotectory effect of PRP contributing as a powerful agent in removal of aluminum accumulation in different tissues at experimental aluminum neurotoxicosis. Experimental model was created by s.c. injection of 1 ml 3% AlCl3. For cytokine determination 80 white male mice (30—40 g) were used. The animals were divided into 3 groups: 1) control, 2) being injected with AlCl3 only; 3) mice were i.p administered PRP (15 or 1.5 mg/animal) on the 4-th day after the injection of AlCl3. The animals were killed 8 days after the AlCl3 injection. Blood serum and supernatants obtained from mice internal organs (intact brain tissue, cerebral cortex, hippocampus, thymus and liver) underwent immunoenzyme analysis (ELISA) for determination of IL-1,2,6, prolactin and IGF-1. The cytokine analysis was performed with DRG International Inc (USA) kits, and prolactin was determined with Microwell™ FSH EIA (USA) kits. IGF-1 was determined using IGF-1 kit (Amersham Biotech, USA). Electron microscopy study was conducted on rats with AlCl3, as well as AlCl3 with preliminary injection of PRP. Tissue slices were taken out of cerebral cortex and hippocampus in the limits of 3 min. Fixation and filling were carried out by the method used in the LCEP in the Institute of Human Morphology of RAMS. The ultrathin slices have been studied by electron microscope JEM-100 CX at 80 kV accelerated voltage. The results of ELISA demonstrated that in aluminum neurotoxicosis PRP in both doses has similar effect on IL-1 level in thymus and liver. The low doses of PRP (1.5 mg) exert more expressed stimulating mediatory effects compared to the higher dose (15 mg). A special interest has to be paid to hypophyseal prolactin, possessing immunomodulatory effects in the CNS as well as in the immune organs, thus stipulating the synthesis of a large spectrum of cytokines. In all tested groups we found interrelation dependence between low levels of prolactin in blood serum, thymus and liver. It should be indicated that in the brains with aluminum neurotoxicosis, prolactin levels decreased 6 times, strongly increasing after PRP exposure. In the same conditions we observed a considerable decrease of IGF-1 mainly in the cerebral cortex, normalized after the injection of lower doses of PRP. By electron microscopy of rat hippocampus, there were neurons of light and dark texture of cytoplasm in 1 h after subcutaneous injection of AlCl3 solution. After 3 days of daily AlCl3 injection in hippocampus, there were neurons with diffuse distribution of Al separate particles. In some myelin nerve fibers we observed saturation with Al molecules. After preliminary PRP injection, we saw no hippocampal neurons with cytoplasm and nuclei edema, containing granules with density of electrons and large inclusions in both cytoplasm and nuclei. Clearly, PRP caused a modulatory effect on the neuroendocrine structures of the hypophisis, directly and/or indirectly stimulating the synthesis of prolactin. We shall emphasize that neurosecretory cytokine from hypothalamus is related with cytokine expression both in the organ studied and in the hypophisis. According to A. Galoyan, there may be intranuclear or even intracellular interrelations between the cytokines and neurotransmitters, which purposed to expression of interleukines, playing important role in the neuro-endocrine regulation.

Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 879-880

Psyhopharmacology & biological narcology

ISSN 1606-8181