Modulatory Role of Resveratrol-Induced Dietary Restriction and Environmental Enrichment on Neurobehavioural Outcome in Young Healthy Mice
ABSTRACT
Dietary Restriction (DR) otherwise known as Caloric Restriction (CR) has been generally defined as consumption of a nutritious diet that is 30% to 40% less in calories compared to an ad libitum diet,
while Environmental Enrichment (EE) is defined as a sustained and progressive increase in cognitive and sensorimotor stimuli with aggregated voluntary physical activity and complex social interactions.
The aim of this experiment was to investigate the modulatory role of Resveratrol induced CR and EE on neurobehavioural responses in young healthy mice.
Twenty-five mice of both sexes were divided into five groups of 5 animals each: group I served as the control and received carboxymethylcellulose (CMC) 50 mg per kg/day orally, group II animals were maintained on every other day feeding, group III animals received Resveratrol 50 mg/kg, suspended in 10 g/L of (CMC) orally per kg/day.
Group IV animals received CMC and were kept in an Enriched Environment while group V animals received Resveratrol 50 mg/kg and were kept in an Enriched Environment. The treatment lasted for a period of four weeks.
On days 26, 27 and 28 of the study period, the animals were subjected to neurobehavioural evaluation of motor coordination, motor strength, learning and memory. Brain and plasma samples were evaluated for lipid profile, lipid peroxidation and antioxidant enzymes.
The results showed a significant increase (P < 0.05) in the transfer latency (acquisition) in the every other day feeding group (69.20 ± 9.03 seconds) compared to the control group (36.80 ± 5.58 seconds).
A significant increase (P <0.05) was observed in the concentration of low-density lipoprotein (LDL) in every other day feeding group (1.72 ± 0.12 mg/dl) and environmental enrichment treatment group (1.73 ± 0.16 mg/dl) when compared to the control group (1.11 ± 0.07 mg/dl).
The results obtained also showed a significant decrease (P < 0.05) in MDA concentration in the Resveratrol treatment group kept in EE (1.50 ± 0.05 IU/L) compared to the control (1.84 ± 0.09 IU/L) and GPx activity in the Resveratrol treatment group kept in EE (41.00 ± 2.02 IU/L) compared to the control (59.00 ± 2.85 IU/L).
In conclusion, the results obtained demonstrated that Resveratrol induced CR and EE have no effects on neurobehavioural responses coupled with some significant alterations in lipid profile, lipid peroxidation and antioxidant enzymes in young healthy mice over a period of four weeks.
TABLE OF CONTENTS
Title Pages
Title page ii
Declaration iii
Certification iv
Dedication v
Acknowledgement vi
Abstract vii
Table of content ix
List of Figures xiv
List of Tables xvi
List of Appendices xvii
List of Abbreviations xviii
CHAPTER 1: INTRODUCTION
Background 1
Statement of the Problem 3
Justification of the Study 4
General Aim 5
Specific Objectives 6
Research Hypotheses 6
CHAPTER 2: LITERATURE REVIEW
Classification of pain 8
Pain recognition and assessment in domestic animals 10
Pain scales 11
Pain and behaviour 12
Mechanism of pain 13
Pain management 19
Oxidative Stress 19
Pain as a stress factor 21
Anaesthesia as a stress factor 22
Antioxidants 23
General Anaesthetics 24
General anaesthesia in goats 25
Nervous system monitoring during general anaesthesia 26
Propofol 27
Mechanism of action of propofol 28
Properties of propofol 29
Pain on injection of propofol 32
Propofol in goats 35
Propofol as an antioxidant 36
Ascorbic Acid 37
Ascorbic acid as an antioxidant 38
Physiological functions of ascorbic acid 39
Intravenous Use of ascorbic acid 42
Ascorbic acid as an ergogenic aid 43
Role of ascorbic acid in pain relief 45
Toxicity and overdose of ascorbic acid 46
CHAPTER 3: MATERIALS AND METHOD
Experimental Animals 47
Anaesthetic Protocol 47
Physiological Parameters 48
Neurobehavioural Study 49
Evaluation of reflexes 49
Behavioural and pain study 49
Haematological Parameters 50
Determination of blood cell counts and packed cell volume 50
Erythrocyte osmotic fragility 50
Biochemical Parameters 51
Determination of Superoxide Dismutase, and Glutathione peroxidise 51
Superoxide dismutase activity 51
Glutathione peroxidase activity 52
Statistical Analysis 52
CHAPTER 4: RESULTS
Effect of Ascorbic Acid and Propofol on Onset and Duration of
Anaesthesia 53
Effect of ascorbic acid and propofol on onset of anaesthesia 53
Effect of ascorbic acid and propofol on duration of anaesthesia 53
Effect of Ascorbic acid and Propofol on Pain Score 53
Effect of Ascorbic Acid and Propofol on Physiological Parameters 54
Effect of ascorbic acid and propofol anaesthesia on heart rate 54
Effect of ascorbic acid and propofol anaesthesia on respiratory rate 54
Effect of ascorbic acid and propofol anaesthesia on rectal temperature 55
Effect of Ascorbic acid and Propofol Anaesthesia on Haematology 62
Effect of Ascorbic acid and Propofol anaesthesia on
Packed Cell Volume (PCV) 62
Effect of Ascorbic acid and Propofol anaesthesia on Leucocyte count 62
Effect of Ascorbic acid and Propofol anaesthesia on
Red Blood Cell count 62
Effect of Ascorbic acid and Propofol anaesthesia on
Haemoglobin concentration 63
Effect of ascorbic acid and propofol anaesthesia on
erythrocyte osmotic fragility 63
Effect of Ascorbic acid and Propofol Anaesthesia on
Serum Biochemistry 70
Effect of ascorbic acid and propofol anaesthesia on
total protein, globulin and albumin concentration 70
Effect of ascorbic acid and propofol anaesthesia on serum Urea levels 75
Effect of ascorbic acid and propofol anaesthesia on
serum antioxidant enzymes 75
Effect of Ascorbic acid and Propofol anaesthesia on serum enzymes 76
Effect of Ascorbic acid and propofol anaesthesia
on Serum electrolyte concentration 84
Effect of Ascorbic Acid and propofol anaesthesia on Reflexes 91
Effect of ascorbic acid and propofol anaesthesia on pedal reflex 91
Effect of ascorbic acid and propofol anaesthesia on swallowing reflex 91
Effect of ascorbic acid and propofol anaesthesia on jaw tone 95
Effect of ascorbic acid and propofol anaesthesia on palpebral reflex 95
CHAPTER 5: DISCUSSION 96 CHAPTER 6: CONCLUSION AND RECOMMENDATIONS
Conclusion 105
Recommendations -105
REFERENCES 106 APPENDICES 131
INTRODUCTION
1.1 Background
Pain is a complex interaction involving sensory, emotional and behavioural factors (Serpell, 2006). Animal pain is an aversive sensory experience representing awareness by the animal of damage or threat to the integrity of its tissues.
It changes the animal‘s physiology and behaviour to reduce or avoid the damage, to reduce the likelihood of its recurrence and to promote recovery (Molony, 1997).
Pain typically involves a noxious stimulus or event that activates nociceptors in the body‘s tissues and conveys signals to the central nervous system, where they are processed and generate multiple responses (NRC, 2009).
Painful stimuli evoke not only discrete sensory perceptions and somatic motor responses, but also marked changes in emotional and autonomic states (Gauriau and Benard, 2002).
The ability to quantify the degree of pain experienced by animals is an important component in the assessment of animal welfare (Barnett, 1997), and may provide useful information on the outcome of intervention to ameliorate pain.
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