Nanoneuroscience: Structural and Functional Roles of the Neuronal Cytoskeleton in Health and Disease

290 Pages·2010·2.95 MB·English

by  Nancy J. Woolf

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Nancy J. Woolf
Avner Priel
Jack A. Tuszynski
Nanoneuroscience
Structural and Functional Roles
of the Neuronal Cytoskeleton
in Health and Disease
With 49 Figures
123
Dr. Nancy J. Woolf Prof. Jack A. Tuszynski
U niversity of California University of Alberta
Los Angeles Department of Physics
Department of Psychology Edmonton AB T6G 1Z2
Lab. NanoNeuroscience Canada
Los Angeles CA 90095-1563 [email protected]
USA
[email protected]
Dr. A vner Priel
University of Alberta
Department of Physics
Edmonton AB T6G 1Z2
Canada
[email protected]
ISSN1618-7210
ISBN978-3-642-03583-8 e-ISBN978-3-642-03584-5
DOI10.1007/978-3-642-03584-5
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Preface
Wewrotethisbooktodescribeanewemergingdisciplinethatintegratesneu-
roscience and nanoscience yielding a unique perspective on the very complex
organization of the material substrate for cognitive processes. Nanoneuro-
sciencefocusesoncomputationallyrelevantbiomoleculesfoundinsideneurons.
Because of recent technological advances at the nanometer scale, scientists
have at their disposal increasingly better ways to study the brain and the
biophysicsofitsmolecules.Duringthe pastcenturythe focusinneurobiology
hasbeenontheneuronanditssynapses.Todaywecanexpandonthesebasic
principles to include the biomolecules that determine operations of synapses
and other computationally relevant functions performed inside dendrites. By
expandingourscopeofknowledgeofwhatparticipatesinneuralcomputation,
we exponentially expand the mind-brain computer analogy through the real-
ization that each neuron has a processing capability conceivably reaching or
evenexceedingthatofasilicon-basedmultiprocessor.Putsimply,oursynapses
feedinformationintoamassivelypowerfulintraneuronalmatrixofcablesand
conduits of information – a system we refer to as Nature’s nanowires.
Although we review all the internal structures inside neurons, a central
themeofthebookishowneurotransmittersactuponreceptormolecules,trig-
gering signal transduction molecules that affect cytoskeletal filaments inside
dendrites of neurons, whereupon cytoskeletal proteins contribute to informa-
tion processing and fundamental operations of neurons. Multiple findings are
presented supporting the notion that naturally occurring nanowires are not
only basic to intracellular transport, but also of fundamental importance to
learning,memory,andpossiblyevenhigherconsciousness.Wepresentourown
research,as well as researchcoming out of other laboratories,with particular
emphasis on the most recent findings. Why do we hypothesize that the inte-
riors of neurons, in particular the cytoskeletalfilaments, play a role in higher
cognitive function and how might they achieve that role? For one, the cy-
toskeletonundergoes structuralchangeduring learning.Second,anabnormal
cytoskeleton appears to be a primary etiological factor contributing to neu-
rological disorders, such as Alzheimer’s disease, and to psychiatric disorders,
VI Preface
suchasbipolaraffectivedisorderandschizophrenia–disordersassociatedwith
deficitsinmemoryfunctionorimpairedmentalstate.Third,cytoskeletalpro-
teins are capable of propagating signals enabling them to form intracellular
circuits that compute and then transmit information form one part of the
neuron to another. This capability is well suited to accommodate cognitive
operations.
This book is intended as an accessible resource for those with interests
in neural computation or brain mechanisms of higher cognition or disease
states. Interested readers might be those with backgrounds in neuroscience,
physics, physiology, psychology, biophysics, biochemistry, computer science,
orbioengineering– orvirtuallyanyonewitha curiosityaboutthe brain-mind
interface and what nanotechnology has revealed and might be expected to
demonstrate in the years ahead. The book is virtually self-contained but we
have provided the reader with numerous references so that more in-depth
studies of individual topics covered in this book can be initiated.
Manycolleagueshavefacilitatedoureffortsinthewritingofthisbook.We
wouldliketothankallcurrentandpastcollaboratorswhohavecollecteddata
or contributed to the core ideas conveyed in this book. First and foremost,
Adele Behar contributed extensively to the research performed through her
generous tangible support and much appreciated encouragement. In fact, we
would like to dedicate this book to her as a token of our appreciation for her
steadfastsupportovera number of yearsandfor her encouragementandmo-
tivation to continue against many odds. Michael Weiner is similarly thanked
for his gracious tangible support and numerous fascinating ideas and sugges-
tions. Stuart Hameroff and others at the Center for Consciousness Studies at
the UniversityofArizonaareowedagreatdebtformanyofthe originalideas
reviewed and extended in this book. Horacio Cantiello and his colleagues at
HarvardUniversityarecreditedwiththosebreakthroughsleadingtothemea-
surement of signal conduction along biomolecules. Travis Craddock is grate-
fully acknowledged for his Master’s thesis work on the double-well potential
in the macromolecule tubulin, a particularly critical piece in the puzzle of
how cytoskeletal proteins might compute outcomes. Lastly, Michelle Hanlon
is thanked for her extensive work on finalizing the manuscript.
Los Angeles, USA Nancy J. Woolf
Edmonton, Canada Jack A. Tuszynski
July 2009 Avner Priel
Contents
1 Introducing Nanoneuroscience as a Distinct Discipline..... 1
1.1 The Definition of Nanoneuroscience........................ 2
1.2 Current Issues in Neuroscience ............................ 4
1.2.1 The Great Mysteries of Neuroscience: Higher
Cognitive Functions ............................... 5
1.2.2 Neurological, Neurodevelopmental, and
Neuropsychiatric Disorders: Prospects for
Nanoneuroscience ................................. 12
1.3 Current Issues in Nanoscience............................. 15
1.3.1 The Origins of Nanoscience......................... 15
1.3.2 The Mission of Nanoscience......................... 16
1.3.3 Nanostructures, Nanoparticles, and Nanodevices ...... 17
1.4 Applications in Nanoneuroscience.......................... 19
1.4.1 Using Nanotechnology to Study Brain
Tissue Response................................... 20
1.4.2 Nanoneuroscience Approaches to Neurological,
Neurodevelopmental, and Neuropsychiatric Disorders... 22
References..................................................... 27
2 Nanoscale Components of Neurons: From Biomolecules
to Nanodevices ............................................ 35
2.1 Intracellular Components of Neurons....................... 36
2.1.1 The Neuronal Membrane and Protein Complexes
Related to Neurotransmission....................... 36
2.1.2 Ion Channels and Ligand-Binding Receptor Proteins... 38
2.1.3 Scaffolding Proteins, Signal Transduction Cascades,
and Cell Adhesion Molecules........................ 45
2.1.4 DNA, mRNA, and the Golgi Apparatus in Neurons:
Transcription, Translation, and Packaging in Synaptic
Vesicles .......................................... 46
VIII Contents
2.1.5 The Neuronal Cytoskeleton......................... 50
2.1.6 Mitochondria in Neurons ........................... 63
2.2 Nanoengineering and Neurons............................. 65
2.2.1 Nanoparticles and Their Interactions with Receptors
and Signal Transduction Molecules .................. 68
2.2.2 DNA Nanodevices................................. 69
2.2.3 Microtubule and Actin Filament Interactions with
Nanomaterials .................................... 69
2.3 Future Directions of Nanodevice-Cell Hybrid Designs ........ 70
References..................................................... 73
3 The Cytoskeleton as a Nanoscale Information Processor ... 85
3.1 Electrical Properties of Actin and Actin Filaments........... 86
3.1.1 The Actin Monomer: Structure, Surface Charge, and
Electric Dipole.................................... 87
3.1.2 Actin Filaments: Counterions and Charge Density
Waves ........................................... 88
3.1.3 Actin Filaments: Electric Cable Properties............ 88
3.2 Electrical Properties of Tubulin and Microtubules ........... 90
3.2.1 Structure, Surface Charge, and Electric Dipole of
Tubulin .......................................... 91
3.2.2 Distinct Tubulin Isoforms Differ in Their Biophysical
Characteristics.................................... 94
3.2.3 Microtubules: Lattice Structure, Elastic Properties,
Surface Charge, and Electric Dipole ................. 96
3.2.4 Microtubules: Ferroelectric and Pyroelectric
Properties........................................ 97
3.2.5 Conductance of Electrical Signals Along Microtubules.. 98
3.3 Linking the Excitable Neuronal Membrane with the
Cytoskeleton: Functional Implications......................101
3.3.1 Actin Filaments Connect the Neuronal Membrane
with the Microtubule Matrix........................101
3.3.2 Does the Intracellular Cytoskeletal Matrix Compute
and Determine Cell Structure and Function?..........103
3.3.3 Information Storage in the Intracellular Cytoskeletal
Matrix: A Role in Memory .........................107
3.4 A Dendritic Cytoskeleton Information Processing Model......112
References.....................................................119
4 Nanocarriers and Intracellular Transport ..................129
4.1 Types of Transport in Neurons............................130
4.2 Motor, Adaptor, and Scaffolding Proteins...................131
4.2.1 Kinesins..........................................131
4.2.2 Dynein...........................................134
4.2.3 Myosin...........................................135
Contents IX
4.3 Mechanisms of Axonal Transport and Nanotechnology .......136
4.3.1 Axonal Transport of Neurotransmitter-Related
Proteins..........................................138
4.3.2 Axonal Transport of Neurotrophins..................140
4.3.3 Axonal Transport of Cytoskeletal Proteins............142
4.4 Dendritic Transport .....................................143
4.4.1 Transport of Neurotransmitter Receptors
into Dendrites ....................................144
4.4.2 Transport of mRNA into Dendrites ..................145
4.5 Cytoskeleton Transport Dynamics with Neural Injury,
Regeneration, and Morphogenesis..........................148
4.5.1 Acute Responses to Neuronal Insult .................149
4.5.2 Transport Regulation in Regeneration and
Morphogenesis ....................................151
4.6 Cytoskeletal Transport in Learning and Memory ............153
4.7 Biophysical Models of Transport ..........................155
4.8 Bioengineering of Transport Molecules and Hybrid Biological
Devices ................................................160
References.....................................................163
5 Nanotechnology, Nanostructure, and Nervous System
Disorders ..................................................177
5.1 Identifying Nanomechanical Dysfunction in Nervous System
Disorders...............................................178
5.2 Neurodevelopmental Disorders: Cytoskeletal Protein
Abnormalities and Impaired Transport .....................178
5.2.1 Fragile X Syndrome: Impaired mRNA Transport ......179
5.2.2 Turner Syndrome: Failure of Dendrite Pruning .......180
5.2.3 WilliamsSyndrome:DeletionsofCytoskeleton-Related
Proteins .........................................181
5.2.4 Autism Spectrum Disorder: Disruptions of MAPs Due
to Deletions of MAP Kinase and Reelin Genes ........182
5.2.5 Rett Syndrome: Decreases in MAP2 Possibly Linked
to Mutations of the MCEP2 Gene ...................183
5.2.6 Down Syndrome: Early and Late Defects in the
Microtubule and Actin Cytoskeleton .................183
5.3 NeurologicalDisorders Involving Nanomechanical Dysfunction 185
5.3.1 Neuromuscular Disorders and Disrupted Axonal
Transport ........................................185
5.3.2 Nanomechanical Dysfunction in Alzheimer’s Disease:
Tauopathies and Impaired Transport.................187
5.3.3 Nanomechanical Dysfunction in Parkinson’s Disease:
Microtubule Instability and Synucleinopathies.........191