Galanin (eBook)

Contents 6
Contributors 8
Galanin: A Multitalented Neuropeptide 12
References 16
Galanin, Galanin Receptors, and Drug Targets 17
Introduction 17
Galanin and Galanin Receptor Agonists 19
Galanin Receptor Subtypes in Regulation of Seizure Threshold, Seizure Initiation, and Maintenance 20
Galanin, Cognition and Neuroprotection in Alzheimer´s Disease 21
Galanin, Mood Regulation and Alcohol Intake 22
Galanin Receptor and Feeding Behavior 22
Galanin in Pain Syndromes 24
Galanin and Tumors 24
Galanin Receptor Ligands in Development 24
References 25
Galanin Acts as a Trophic Factor to the Central and Peripheral Nervous Systems 34
Introduction 35
Nociceptor Survival 35
Neurite Outgrowth 36
Neuronal Survival in the CNS 38
Neuroprotection 38
Analysis of the Enhancer Regions of the Galanin Gene that Confer Responsiveness to Axotomy 42
Galanin- and GalR2-Dependent Signalling Cascades 42
Conclusion 44
References 44
Galanin and Spinal Pain Mechanisms: Past, Present, and Future 48
Galanin and Galanin Receptors in Sensory Neurons and in the Spinal Cord 48
Pharmacology of the Effects of Galanin on Spinal Nociception Under Normal Condition 49
The Physiological Role of Galanin in Nociception Under Normal Condition and After Nerve Injury 51
The Potential of Galaninergic Drugs as Analgesics 54
References 54
Galanin Family of Peptides in Skin Function 60
The Galanin Peptide Family 61
Nervous Innervation and Neurogenic Inflammation 61
Immune System and Inflammation of the Mammalian Skin 62
Proliferation and Wound Healing 64
Future Perspectives 65
References 66
Galanin in Glia: Expression and Potential Roles in the CNS 69
Experimental Central Nervous System Injury 69
Potential Roles for Glial Galanin Expression in Limiting CNS Injury 71
Regulation of Glial Galanin Expression and Secretion 73
White Matter Development 73
Conclusions 75
References 75
Galanin and the Neuroendocrine Axes 78
Introduction 78
Parvicellular (hypophysiotropic) and Magnocellular Galanin Systems 79
Pituitary Galanin 79
Galanin and the Hypothalamic-Pituitary-Gonadal (HPG) Axis 80
Galanin and the Hypothalamic-Pituitary-Adrenal Axis 83
The Role of Galanin in the Neuroendocrine Regulation of Growth Hormone Secretion 84
The Role of Galanin in the Neuroendocrine Regulation of Prolactin Secretion 86
The Role of Galanin in the Neuroendocrine Regulation of Thyroid-Stimulating Hormone Secretion 87
The Role of Galanin in Osmotic Regulation and Water Intake 88
Concluding Remarks 88
References 89
Galanin and Consummatory Behavior: Special Relationship with Dietary Fat, Alcohol and Circulating Lipids 93
Introduction 94
Galanin and Consummatory Behavior 94
Stimulatory Effect of GAL on Food Intake and Preference for a Fat-Rich Diet 94
Positive Relationship Between PVN GAL Expression and Dietary Fat 95
Positive Relationship Between GAL and Ethanol Intake 97
Role of GAL in Stress-Induced Eating 97
Relationship Between Galanin and Other Neurotransmitters 98
GAL in Relation to NE 98
GAL in Relation to 5-HT 99
GAL in Relation to DA 99
GAL in Relation to ACh 100
Galanin and Opioid Peptide Interactions in the Hypothalamus 101
Close Relationship Between Galanin and Endogenous Lipids 102
Involvement of TG in the Relationship Between GAL and Dietary Fat 102
Involvement of TG in Fat-Induced Overeating 102
Role of TG and GAL in Relationship Between Fat and Ethanol Intake 103
Relationship Between Galanin and Gonadal Steroids 104
Role of GAL in Overeating During Proestrous in Adult Female Rats 104
Close Relationship Between GAL and Reproductive Hormones in Controlling Fat Intake in Females 104
Role of GAL in Controlling Eating Behavior at Puberty 105
Galanin and Neuronal Development 106
Effects of Prenatal High-Fat Diet Exposure on GAL and Neurogenesis 106
Role of GAL as a Trophic Factor 107
Role of GAL in Neuroprotection 107
Role of GAL in Neuronal Stability 108
Summary and Conclusion 108
References 109
Neurochemical Modulation of Central Cardiovascular Control: The Integrative Role of Galanin 118
Introduction 119
Role of Galanin in Central Cardiovascular Regulation 120
GAL Fragments 122
Galanin/Classical Neurotransmitter Interactions in Central Cardiovascular Regulation 124
GalaninR/5-HT1A Interactions 124
GalaninR/a2-Adrenoreceptor Interactions 124
Galanin/Neuropeptide Interactions in Central Cardiovascular Regulation 125
GalaninR/Angiotensin II AT1 Receptor Interactions 126
GalaninR/Neuropeptide Y R Subtype Interactions 127
Conclusions 129
References 133
Galanin Impairs Cognitive Abilities in Rodents: Relevance to Alzheimer´s Disease 137
Introduction 137
References 141
Neuroprotective Role for Galanin in Alzheimer´s Disease 146
Introduction 146
Galanin in Alzheimer´s Disease 147
Potential Triggers of GAL Plasticity in AD 149
Neuronal Origin of GAL Hyperinnervation in AD 150
Galanin Plasticity as a Detrimental Factor in AD 152
Galanin Plasticity as a Neuroprotective Factor in AD 153
Galanin Receptors as Therapeutic Targets for AD 158
Conclusions 159
References 159
Galanin, Galanin Receptor Subtypes and Depression-Like Behaviour 166
Introduction 166
Depression - Monoamine Hypotheses 167
Current Therapy of Mood Disorders and Its Limitations 167
Peptidergic Approaches in Development of Novel Antidepressants 168
Galanin and Galanin Receptors in the Brain 168
Modulatory Effects of Galanin on NA and 5-HT Neurotransmission 169
Interaction of Galanin and 5-HT1A Receptors 170
Galanin and Depression: Pharmacological Evidence 172
Galaninergic Mechanisms in Animal Models of Depression 174
The Role of Different Galanin Receptor Subtypes 175
Galanin Systems in Depression: Potential Mechanisms 176
Concluding Remarks and Perspectives 178
References 179
Galanin and Epilepsy 185
Introduction 185
Galanin in Temporal Lobe Epilepsy 186
Differential Involvement of Galanin Receptor Subtypes in the Modulation of Seizure Activity 190
Signaling Cascades that Mediate Anticonvulsant Effects of Galanin 191
Extrahippocampal Galanin as a Modifier of Limbic Seizures 191
A Prospect for Galanin-Based Antiepileptic Drugs 192
Conclusions 193
References 193
Galanin and Addiction 197
Interactions Between Neuropeptides and Addictive Drugs 198
Introduction: Feeding Peptides that Influence Behaviors Related to Drug Abuse 198
Behavioral Studies: Effects of Galanin on Opiate Locomotion and Reward 198
Effects of Galanin on Neurotransmitters and Signaling Molecules Involved in Drug Addiction 199
Regulation of the Dopaminergic and Cholinergic Systems by Galanin 199
Galanin-Mediated Modulation of Intracellular Signaling Pathways Following Morphine Administration 201
Galanin and Alcohol 202
Galanin and Opiate Withdrawal 203
Behavioral Studies 203
Potential Mechanisms Underlying the Effects of Galanin on Morphine Withdrawal 203
Galanin-Mediated Biochemical Changes Following Opiate Withdrawal 204
Summary and Conclusions 204
References 205
Galanin Systems and Ischemia: Peptide and Receptor Plasticity in Neurons and Oligodendroglial Precursors 211
Galanin and Galanin Receptors in the Central Nervous System 212
Presence and Role of Galanin in Neurons and Precursor Cells 212
Neurogenesis in Adult Brain: Induction by Injury and Identity of Regulatory Factors 212
Activation of Precursor Cells by Focal Cerebral Ischemia 213
Effects of Focal Ischemia on Galanin and Galanin Receptor Expression in Cortex 213
Middle Cerebral Artery Occlusion 213
Analysis of Galanin and Galanin Receptor Alterations 214
Cortical and Sub-cortical Galanin Expression: Basal Levels and Effect of MCAo 214
Galanin mRNA 214
Galanin Immunoreactivity 215
Cortical/Sub-cortical Galanin Receptor Expression: Basal Levels and Effect of MCAo 218
Cortical GalR1 and GalR2 mRNA Expression After MCAo 218
Increased Galanin Binding Levels in Cortex After MCAo 218
Neuronal and Glial Responses Following Focal Ischemia: Role of Galanin 218
References 220
The Galanin System in Cancer 224
Value of Neuropeptides in Cancer Detection and Treatment 225
Pheochromocytoma 226
Neuroblastic Tumours 228
Pituitary Adenoma 229
Gastrointestinal Cancer 231
Squamous Cell Carcinoma 231
Diverse Tumours and Tumour Cell Lines 232
Signal Transduction of Galanin Receptors in Tumour Cells 234
Summary of Galanin Receptor-Mediated Effects in Tumour Cells 236
References 237
Galanin Systems in Non-mammalian Vertebrates with Special Focus on Fishes 243
Introduction 243
Galanin Gene and mRNA 244
Protein 247
Tissue Distribution of Galanin 248
Physiological Functions 249
Fish 250
Amphibians 251
Reptiles 251
Birds 252
Galanin Receptors 252
Galanin Related Peptides 253
Conclusions 256
References 257
Galanin-Like Peptide: Neural Regulator of Energy Homeostasis and Reproduction 263
Discovery of Galanin-Like Peptide: Relationship to Galanin 264
Distribution of GALP 265
Expression of GALP mRNA and Protein in the CNS 265
Expression of GALP mRNA and Protein in the Periphery 265
Phenotype and Targets of GALP-Expressing Neurons 266
Regulation of the GALP Gene in the CNS 267
Central Actions of GALP 269
The Effect of GALP on Feeding, Body Weight and Metabolism 269
The Effect of GALP on Reproduction 271
Neural Mechanisms of GALP Actions 272
GALP-NPY and Orexin Interactions 272
GALP-Dopamine Interactions in the mPOA 273
GALP-Interleukin-1 Interactions 274
Evidence for GALP-Specific Receptors 275
Summary and Conclusion 275
References 276
Index 281