ProCognitive Properties of the Immunomodulatory P

Authors: Marta Lemieszewska Marta JakubikWitkowska Bartłomiej Stańczykiewicz Aleksandra Zambrowicz Agnieszka Zabłocka Antoni Polanowski Tadeusz Trziszka Joanna Rymaszewska

Publish Date: 2016/03/14

Volume: 64, Issue: 5, Pages: 425-434

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Abstract

The study aimed to assess the effect of the polypeptide Y complex Yolkin isolated from chicken egg yolk on behavioural and cognitive functions It also aimed to compare this activity with colostrumderived substances Colostrinin Coloco which have a confirmed impact on learning and memory In the study the effect of Yolkin administered to rats of different ages who performed various tasks involving spatial and episodic memory motor functions and exploratory behavior was assessed The experiment was carried out in rats which were 6 and 12 months old Two different doses of the studied specimens based on previous comparative studies and two different routes of administration oral and retroperitoneal were used A series of behavioural tests were carried out including an open field test a novel object recognition test and a Morris water maze They were used to evaluate the impact of the studied specimen on improving locomotor function and exploratory behaviour preventing their decline and assess the functioning of episodic and spatial memory in aging rats The administration of Yolkin gave distinct effects compared to colostrumderived substances although confirmed its suggested procognitive action Therefore it may be used to enhance cognitive functions and inhibit the progression of dementia in the course of neurodegenerative disordersCognitive disorders affecting memory and learning abilities normally occur in the process of aging mild cognitive impairment and in Alzheimer disease Lindeboom and Weinstein 2004 Pepeu 2004 The use of animal models including transgenic mice and rats and sensitive tests allows a precise detection of key behavioural markers of progressive degenerative disorders occurring in the brain It also enables an analysis of the efficacy of therapeutic agents Do Carmo and Cuello 2013 Preclinical studies are most often carried out on rats due to their complex behaviour easier learning of cognitive tasks and their lower levels of aggression compared to mice Rats also cope better when carrying out complex instrumental tasks and exhibit less stress when placed in water Iannaccone and Jacob 2009For nearly 75 years studies have been carried out on substances delaying symptoms of brain ageing and neurodegenerative disorders The antioxidative and antiinflammatory properties Xiao and Tundis 2013 of pituitary peptides de Wied 1997 Lukas et al 2012 and numerous natural bioactive substances of plant such as coffee or animal such as marine crustacean origin has been demonstrated on animal models ShukittHale et al 2013 Milk is characterized as a product of animal origin with a high content of prolinerich protein precursors Proline is an amino acid with a characteristic heterocyclic compound which determines its high chemical activity including its antioxidative capability Camfield et al 2011 The mammary gland secretions during lactation especially of colostrum are of particular interest in terms of their biological activity and potential health benefits Colostrum contains peptides and proteins rich in proline which support development and the immune system Zimecki and Artym 2013The biochemical and immunological properties of colostrum and its components have been tested in both animal models and in vitro Darewicz et al 2011 A prolinerich polypeptide complex PRP later named Colostrinin CLN was isolated from ovine colostrum in 1974 Janusz et al 1974 Colostrinin was found to have antiinflammatory and antioxidant properties based on cell culture and in vivo studies It was also found to regulate growth as well as differentiation of lymphocytes and inhibit pathological conditions associated with βamyloid aggregation Boldogh and Kruzel 2008 Janusz and Zabłocka 2010 A nonapeptide which is a component of the PRP complex was also found to have antiaggregating properties Janusz et al 2009 The CLN complex was also found to have strong neuroprotective activity inhibiting nerve cell apoptosis induced by the deposition of toxic amyloid DouraghiZadeh et al 2009 Schuster et al 2005 Colostrinin improves learning and memory in rats delays the progression of dementia and loss of long term memory in aging animals Popik et al 1999 2001 Stewart and Banks 2006 Positive results of preliminary clinical trials on patients with Alzheimer disease in which from a total of 15 patients receiving oral CLN at a dose of 100 μg eight improved according to the MiniMental State Examination while disease symptoms stabilized in the remaining seven patients Leszek et al 1999 These results were confirmed in multicenter double blind clinical studies performed on 105 patients Bilikiewicz and Gauss 2004The discovery of procognitive and therapeutic properties of the CLN prompted the search for other substances with similar biochemical characteristics which would also be widely available and contain an appropriate amount of biologically active and bioavailable ingredients These substances should also be easy to identify isolate and process pharmaceutically Polypeptide complexes associated with immunoglobulin antibodies found in egg yolk are functionally equivalent to those found in colostrum Kim et al 2000 Tini et al 2002 A polypeptide complex associated with a major avian immunoglobulin class IgY present in egg yolk called Yolkin Y was found and isolated in the course of studies Polanowski et al 2012 Its similarities to CLN in terms of immunoregulatory properties including stimulation of cytokine secretion have been shown These properties may also indicate a similarity between Yolkin and CLN in terms of the procognitive activity Kruzel et al 2001 The present study aimed to assess the behavioural and cognitive effects of Yolkin—immunomodulatory peptide complex isolated from chicken egg yolk and to compare it with colostrumderived substances—Colostrinin and recently separated ColocoPRP Polanowski et al 2013 2015Animals used in the study were provided by the animal house located at the Division of Pathomorphology at the Wroclaw Medical University All experiments were conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals and approved by the 1st Local Committee for Experiments with the Use of Laboratory Animals Wroclaw Poland Animals were killed by decapitation under anesthesia with ketamine 05 mL of 100 mg/kg body weight at a dosage of 055 mL/100 g body weightMale Wistar rats n = 120 at the age of 6 months and body weight ranged from 300 to 350 g were divided into two groups n = 60 housed in pairs in the standard mediumsized laboratory rat cages ca 45 × 35 × 20 cm One group received the preparations in the form of intraperitoneal ip injections and the other in the form of an oral aqueous solution Each group was divided into subgroups receiving the following preparations diluted in 05 mL of vehicle 09  NaCl per rat Yolkin at 100 μg/kg of body weight Y100 Yolkin at 10 μg/kg of body weight Y10 Colostrinin at 50 μg/kg of body weight CLN ColocoPRP at 50 μg/kg of body weight Col and the control group receiving either an ip 09  NaCl S or an oral aqueous solution of bovine serum albumin BSA at 100 μg/kg of body weight During the oral administration of ca 100 mL of liquid per rat per day the rats had to drink the bottle with the study solution afterwards it was replaced with tap water It was not intended to determine exact dosage as the oral administration needs to have the nature of supplementation Subgroups and preparations were matched randomly and blinded by experimenter’s assistant before the experiment so the experimenter was blind to the treatment conditions

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