MODULATORY EFFECT OF AQUEOUS EXTRACT OF PHOENIX DACTYLIFERA LINNFRUIT ON COGNITION IN SWISS ALBINO MICE Â
ABSTRACT
Phoenix dactylifera fruits possess essential properties such as analgesic, antioxidant, and nephroprotective activity but there is paucity of information on researches centered on the benefits of Phoenix dactylifera in learning and memory. This study was designed to evaluate the effects of Phoenix dactylifera fruit extract on spatial learning and memory using neurobehavioral paradigms of Morris water, Barnes, and elevated plus mazes as well as evaluation of acetylcholinesterase enzyme activity of the brain tissues of the mice studied. Seventy five mice of both sexes were used for the study and divided into five groups of 5 mice each. Group 1 (distilled water 10 ml/kg) served as control, group 5 (Piracetam 100 mg/kg) served as positive control. Groups 2-4 were treated withPhoenix dactylifera extract 1000, 500 and 250 mg/kg respectively. Treatment with aqueous extract of Phoenix dactylifera and Piracetam was done 1 hour prior to the experiment daily for three days (in Morris water and Barnes mazes) and two days (in elevated plus maze). Results obtained from this study revealed that Phoenix dactylifera fruit (1000 mg/kg) impaired learning of mice in Morris water maze (p<0.05), but did not impair memory in Morris water maze, Barnes maze and elevated plus maze. No statistically significant difference was seen between control group and Phoenix dactylifera treated groups in acetylcholinesterase activity in Morris water, Barnes and elevated plus mazes, but statistically significant difference exist between control group and Piracetam treated group in acetylcholinesterase activity (p>0.05). No strong correlation was observed between probe parameters of neurobehavioral paradigms (frequency of platform crossings, retention and correct head dips in Morris water, Barnes and elevated plus mazes respectively) and acetylcholinesterase activity. Acute treatment with aqueous extract of Phoenix dactylifera fruit impaired learning in Morris water maze and has no effect on memory in Morris water, Barnes and elevated plus mazes
Table of Contents
Page
Title Page i
Declaration… ii
Certification… iii
Dedication… iv
Acknowlegements… v
Table of Contents… vi
List of Tables… ix
List of Figures… x
List of Plates… xi
List of Appendices… xii
Abstract… xiii
INTRODUCTION…1
Statement of Research Problems…2
Justification…3
Research Hypothesis3
Aim and Objectives3
LITERATURE REVIEW5
Learning and Memory5
Short-Term Memory5
Long-Term Memory6
Declarative Memory6
Implicit Memory7
Spatial Cognition…7
Memory Enhancers9
Academic Doping9
Synaptic Plasticity10
Biochemical Mechanism of Synaptic Plasticity10
Date Palm Fruit (Phoenix dactylifera)…13
Date Palm Fruits and Cognition…18
Date Palm Fruits and Other Components of Nervous System…19
MATERIALS AND METHODS…23
Animals…24
Drug Preparation…24
Neurobehavioral Assay24
Morris Water Maze24
Elevated Plus Maze for Memory27
Barnes Maze29
Biochemical Analysis…31
Brain Tissue Preparation…31
Acetylcholinesterase Assay Kit…31
Acetylcholinesterase Assay32
Statistical Analysis32
RESULTS33
Assessment of Visio-Spatial Long Term Memory using Morris Water Maze33
Assessment of Visio-Spatial Long Term Memory using Elevated Plus Maze36
Assessment of Visio-Spatial Long Term Memory using Barnes Maze36
Acetylcholinesterase Enzyme Activity48
Acetylcholinesterase Enzyme Activity of Mice Used in Morris Water Maze48
Acetylcholinesterase Enzyme Activity of Mice Used in Elevated Plus Maze48
Acetylcholinesterase Enzyme Activity of Mice Used in Barnes Maze48
5.0 DISCUSSION… 54
Summary57
Conclusion…57
Recommendations…57
Contribution to Knowledge58
REFERENCES 59
Appendices… 67
CHAPTER ONE
Introduction
One of the major functions of the brain is the flexible adaptation to our ever-changing environment. The brain possesses executive circuits which do not only monitor and maintain current behavioral goals but also incorporate new goals and rules. This updating can come in the form of a quick integration of previously acquired knowledge when a well-known stimulus informs an animal of a change in reward contingencies. Hence, such updating requires new learning.Higher cognitive abilities evolved largely in mammals (Victoria et al., 2014).
Cognitive neuroscientists consider memory as the retention, reactivation, and reconstruction of the experience-independent internal representation (Schwabe and Wolf, 2010). The major challenge of neuroscientists today is identifying therapies or mechanisms that can treat or reverse the effects of  memory complaints and other neurodegenerative disorders.  Date palm (known as Phoenix dactylifera) has been used intreatment of various nervous disorders and memory complaint (Vyawahare et al., 2009), such as Parkinson‘s disease via acting as dopamine agonist (Ali et al., 2014), Alzheimer‘s and Vascular dementiavia its protective role in cerebral hypoperfusion (Rohini et al., 2014).
Brain areas involved in the neuroanatomy of memory include the hippocampus, the amygdala, the striatum, or the mammillary bodies which are thought to be involved in specific types of memory. For example, the hippocampus is believed to be involved in spatial learning and declarative learning, while the amygdala is thought to be involved in emotional memory (Labark and Cabeza, 2006). Prefrontal cortex and basal ganlia play vital role in storing working memory (Fiona and Torkel, 2008). The mechanism via which basal ganglia store working memory might
be via dopamine modulation in ventral tegmented area and substantia nigra (Karin and Daphna, 2011).
Today, a major point of concern for research in the pharmaceutical sciences isfinding unique and efficient compounds of natural origin. Plants have been seen to possess the potential to be excellent lead structures and to serve as a basis of promising therapeutic agents for treatmentof diseases (Jabeena et al., 2014).Also, restoration and development of traditional Medicine should be a main concern of health plan, which is in line with WHO‘s call for returning to use of traditional treatments to those countries with a history of traditional medicine (Sahar et al., 2013). Date fruit from date palmhas been used as food for over 6000 years. Although precise origin is obscure historically, but there is evidence its' dating to 4000 BC. Resources confirm that it is indigenous to Northeast Africa. It grows a wide belt from the Atlantic Ocean through the Sahara, the Arabian Peninsula, into Iran and Pakistan (Sahar et al., 2013).
Statement of Research Problems
Understanding the variations in encoding and retrieving information among individuals of the same sex and age are parts of the challenges of neuroscientists today. These variations in memory may be associated with diet or ability of an individual to utilize his neurons.Today, cognitive enhancement is one of the most controversial topics in neuroscience. Academic doping is the off-label use of nootropics for the purpose of enhancing cognitive ability or academic success (Lucke et al., 2014). The use of drugs for academic doping are influenced positively or negatively by several factors. Among them are personal characteristics, drug characteristics, and characteristics of the social context. Numerous researches had shown that nootropics such as piracetam and cholinergics (e.g choline, meclofenoxate, galantamine) enhance cognition
(McDaniel et al., 2002; Gualtieri et al., 2002). These drugs have many side effects, not easily affordable and some are used as substances of abuse by students in colleges(Kimberly and Wen, 2014). Hence, alternatives are really needed.Phoenix dactyliferais a fruit acceptable and easily affordable by most people because of its sweet taste and cheapness. This research work will evaluate the effects of Phoenix dactylifera on cognition in mice.
Justification
Many researches have been conducted on the effects of Phoenix dactylifera in organ systems including the nervous system by Asadi-Shekari et al., (2008), Panahi et al., (2008), and Masoumeh et al., (2014) among others.Phoenix dactylifera was found to cause significant increase in motor co-ordination and analgesic activities (Vyawahare et al., 2009).To what extent Phoenix dactylifera increases cognition is not well scientifically established. This study was specificallycarried out on cognition to investigate the traditionally claimed that Phoenix dactylifera has been used in treatment of various nervous disorders and memory complaints.The significant of this study centered on finding alternative source of cognitive enhancement from dietary sources, as well as reducing drug abuse by the students in colleges for academic doping.
Research Hypothesis
Aqueous extract of Phoenix dactylifera fruits has no effect on cognition in mice
Aim and Objectives
Aim
The aim of this research is to determine the effect of aquoeus extract of Phoenix dactylifera on cognition in mice.
Objectives
Specific objectives of the study are:
(i) To assess the effects of Phoenix dactylifera on visio-spatial memory using Morris water, Barnes and elevated plus mazes.
(ii) To determine the effect of Phoenix dactyliferaon acetylcholinesterase enzyme activity in brain of mice using acetylcholinesterse assay kit.
.