Transcription Factors CREB and NF-κB: Involvement in Synaptic Plasticity and Memory Formation


by

Benedict C. Albensi

DOI: 10.2174/97816080525781120101
eISBN: 978-1-60805-257-8, 2012
ISBN: 978-1-60805-418-3



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Indexed in: Chemical Abstracts, Scopus, EBSCO.

The main theme of this book is to critically survey the role of two recognized protein molecules (i.e., transcription factors) in proc...[view complete introduction]

Table of Contents

About the Editor

- Pp. i

Benedict C. Albensi

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Foreword

- Pp. ii

Brian R. Christie

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Preface

- Pp. iii

Benedict C. Albensi

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List of Contributors

- Pp. iv-v (2)

Benedict C. Albensi

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Regulation of Synaptic Plasticity and Long-Term Memory by CREB: Implications for Targeting Memory Disorders Including Alzheimer’s Disease and Rubinstein-Taybi Syndrome

- Pp. 3-21 (19)

Asim J. Rashid and Sheena A. Josselyn

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The Role of CREB in Neuronal Plasticity, Learning and Memory, and in Neuropsychiatric Disorders

- Pp. 22-42 (21)

Angela Fontan-Lozano, Rocio Romero-Granados, Eva M. Perez-Villegas and Angel M. Carrion

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Transcriptional Profiling of Hippocampal Memory-Associated Synaptic Plasticity: Old Friends and New Faces

- Pp. 43-65 (23)

Niamh C. O’Sullivan,, Graham K. Sheridan and Keith J. Murphy

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Roles for NF-κB in Regulating Gene Expression in Synaptic Plasticity and Memory

- Pp. 66-78 (13)

Gary Odero, Wanda Snow, Kunjumon Vadakkan and Benedict C. Albensi

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NF-κB Proteins in Adult Neurogenesis: Relevance for Learning and Memory in Physiology and Pathology

- Pp. 79-96 (18)

Mariagrazia Grilli and Vasco Meneghini

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NF-kB Transcription Factor: A Model for the Study of Transcription Regulation in Memory Consolidation, Reconsolidation and Extinction

- Pp. 97-112 (16)

Arturo Romano

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NF-κB in Neurons-Mechanisms and Myths

- Pp. 113-129 (17)

Steven W. Barger and Xianrong R. Mao

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Index

- Pp. 130-133 (4)

Benedict C. Albensi

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Foreword

The world was originally introduced to the concept of synaptic plasticity over 60 years ago, when Dr. Donald Hebb first clearly defined a physiological mechanism for learning and memory in his seminal work “The Organization of Behavior”. It took another 20 years for Bliss and Lomo to scientifically validate Hebb’s postulate, and show that neurons could alter their ability to communicate with one another in a persistent manner. Together, these works started off what has grown to become the field of synaptic plasticity. The years following the initial discovery were exciting times for learning and memory young researchers like myself, and each discovery over the next 20 years seemed to push us closer to elucidating the biological mechanisms responsible for memory formation. This seemed particularly true in the mid-1980’s when the NMDA receptor was being heralded as the key to learning and memory processes. However, more recently it has become obvious that the activation of membrane receptors is only the first step in a cascade of post-synaptic events that ultimately results in genomic changes. While it remains unclear whether memories reside in our genes, it is clear that several gene transcription factors play a role in determining how easily and reliably changes in neuronal communication can be established. The works included in this book help to explain the evidence for two specific transcription factors, cAMP response element-binding (CREB) and NF-κB, being involved in synaptic plasticity. Furthermore, recent evidence is presented for how alterations in the normal functioning of these transcription factors can play a role is some specific disease processes. These topics included are essential reading for any student of the mind, and particularly for those of us engaged in synaptic plasticity research.

Brian R. Christie

Division of Medical Sciences, University of Victoria, Victoria, BC

The Island Medical Program, University of British Columbia, Victoria, BC


Preface

Transcription factors are specialized proteins that bind to specific DNA sequences, thereby controlling the movement (a.k.a. transcription) of genetic information from DNA to mRNA. In so doing, transcription factors can promote or repress the recruitment of RNA polymerase to specific genes thereby regulating gene expression.

Synaptic plasticity is the capacity of the connections between neurons to change in strength in response to alterations in synaptic transmission and other cellular signals. So-called plastic change is possible as a result of several mechanisms that function co-operatively in the synaptic region and results in morphological change. The formation of memory is theorized to be associated with and driven by mechanisms of synaptic plasticity.

The main aim of the authors for this book was to critically survey the role of two recognized transcription factors in processes of synaptic plasticity and memory. In addition, the authors provided recent data from their own labs and in some cases provided a perspective relevant to specific CNS diseases and potential drug targets. Historically, the transcription factor cAMP response element-binding (CREB) has been the most well documented transcription factor shown to play a role in synaptic plasticity and memory. CREB has several functions, but its most notable function has to do with the formation of long-term memories where knock out of this protein not only impairs memory, but also has a negative effect on cell survival. More recently, other transcription factors, such as CCAAT/enhancer binding protein (C/EBP), early growth response (Egr) protein, activator protein 1 (AP-1), and nuclear factor kappa B (NF-κB) have been implicated in synaptic plasticity and memory as well. Of these, scientific literature on NF-κB’s theorized role in synaptic plasticity and memory is growing rapidly. Interestingly, in some recent studies CREB and NF-κB have also been shown to interact with each other where both contribute in a cooperative fashion to the initiation of gene expression.

This book is divided into seven chapters. In the first two chapters, CREB is reviewed and roles for this protein are evaluated not only in normal long term memory, but also in a context of memory impairment in disease states such as Alzheimer’s disease (chapter one), Rubinstein-Taybi syndrome (chapter one), and some neuropsychiatric disorders (chapter two), etc. The third chapter serves as a bridge for our two highlighted transcription factors, where the author presents a synthesized discussion of the literature on CREB and NF-κB and also on other transcription factors that are relatively unrecognized at the time of this writing. In the fourth chapter, the potential role of NF-κB in synaptic plasticity and memory is discussed and recent evidence for its participation from several models is presented. In chapter five, a more specific role for NF-κB is considered that involves adult neurogenesis. The sixth chapter discusses NF-κB and specific mechanisms of transcriptional regulation and puts into perspective how NF-κB may play a role in several forms of memory including, memory consolidation, reconsolidation and extinction.

The final chapter serves well not only to summarize and question NF-κB’s role in synaptic plasticity and memory, but also to point out important technical considerations that may have influenced (rightly or wrongly) many past studies in this field.

We are living in an exciting time for memory research. The last several decades have seen an explosion in scientific data and literature that have contributed to our understanding of the neurological basis of memory. In spite of this plethora of information many outstanding questions still remain: What processes underlie the formation of new memories and the establishment of long term memory? What mechanisms determine the strength of memory? Which molecules play essential roles in these processes? How do the transcription factors CREB and NF-κB contribute to processes of long term memory? The chapters in this book attempt to address some of these most interesting, but unanswered questions.

Benedict C. Albensi, Ph.D.

University of Manitoba

Canada

List of Contributors

Editor(s):
Benedict C. Albensi
University of Manitoba
Canada




Contributor(s):
Benedict C. Albensi
Division of Neurodegenerative Disorders
St. Boniface General Hospital Research Centre
351 Tache Ave, St. Boniface Research Centre, R4050
Winnipeg
MB, R2H 2A6
R2H 2A6Canada
/
Department of Pharmacology and Therapeutics
University of Manitoba
Winnipeg, MB, A203 Chown Bldg., 753 McDermot Avenue
Winnipeg
MB, R3T 2N2
R2H 2A6Canada


Steven W. Barger
Department of Geriatric
Department of Neurobiology and Developmental Sciences
University of Arkansas for Medical Sciences
Little Rock AR, 72205
USA
/
Geriatric Research Education and Clinical Center
Central Arkansas Veterans Healthcare System
Little Rock AR, 72205
USA


Ángel M. Carrión
División de Neurociencias
Universidad Pablo de Olavide
Carretera de Utrera Km. 1
Sevilla-41013, Spain



Ángela Fontán-Lozano
División de Neurociencias
Universidad Pablo de Olavide
Carretera de Utrera Km. 1
Sevilla-41013, Spain



Mariagrazia Grilli
DiSCAFF, University of Piemonte Orientale “A. Avogadro” & DFB Center
Laboratory of Neuroplasticity and Pain
Novara , 28100
Italy


Sheena A. Josselyn
Program in Neurosciences & Mental Health
Hospital for Sick Children Research Institute
555 University Ave
Toronto
ON, M5G 1X8
Canada
/
Department of Physiology
University of Toronto
1 King's College Circle
Toronto
ON, M5S 1A8
Canada


Xianrong R. Mao
Department of Anesthesiology
Washington University School of Medicine
St. Louis MO, 63110
USA


Vasco Meneghini
Applied Neurotherapeutics Research Group
UCD School of Biomolecular and Biomedical Science
Conway Institute, University College Dublin
Belfield
Dublin 4
Ireland


Keith J. Murphy
School of Electrical and Electronic Engineering
Nanyang Technological University
Block S1, Level B1C, Room 100
Nanyang Link, 639798
Singapore


Gary Odero
Division of Neurodegenerative Disorders
St. Boniface General Hospital Research Centre
351 Tache Ave, St. Boniface Research Centre
Winnipeg MB
R2H 2A6
Canada


Niamh C. O’Sullivan
Applied Neurotherapeutics Research Group
UCD School of Biomolecular and Biomedical Science
Conway Institute, University College Dublin
Belfield
Dublin 4
Ireland


Eva M. Pérez-Villegas
División de Neurociencias
Universidad Pablo de Olavide
Carretera de Utrera Km. 1
Sevilla-41013
Spain


Asim J. Rashid
Program in Neurosciences & Mental Health
Hospital for Sick Children Research Institute
555 University Ave
Toronto ON
M5G 1X8
Canada


Arturo Romano
Laboratorio de Neurobiología de la Memoria
Departamento de Fisiología, Biología Molecular y Celular
Facultad de Ciencias Exactas y Naturales
Universidad de Buenos Aires,
IFIBYNECONICET
Ciudad Universitaria
Pab. II, 2do Piso (1428)
Buenos Aires
Argentina


Rocío Romero-Granados
División de Neurociencias
Universidad Pablo de Olavide
Carretera de Utrera Km. 1
Sevilla-41013
Spain


Graham K. Sheridan
Applied Neurotherapeutics Research Group
UCD School of Biomolecular and Biomedical Science, Conway Institute
University College Dublin
Belfield
Dublin 4
Ireland


Wanda Snow
Division of Neurodegenerative Disorders
St. Boniface General Hospital Research Centre,
351 Tache Ave
St. Boniface Research Centre
R4050, Winnipeg
MB, R2H 2A6
Canada


Kunjumon Vadakkan
Division of Neurodegenerative Disorders
St. Boniface General Hospital Research Centre,
351 Tache Ave
St. Boniface Research Centre
R4050, Winnipeg
MB, R2H 2A6
Canada




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