Neuro-Urology Research: A Comprehensive Overview

Front Cover
Neuro-Urology Research
Neuro-Urology Research
Copyright
Contents
Contributors
About the editor
Preface
Acknowledgments
1 - Neuro-urology research: a comprehensive overview
	Outline
		Chapter 1—Neuro-urology research: a comprehensive overview
		Chapter 2—Barrington\'s nucleus: a century of progress identifying neurons that control micturition
		Chapter 3—Voluntary versus reflex micturition control
		Chapter 4—The bladder as a readout in neuroscience research
		Chapter 5—How treatment of lower urinary tract symptoms can benefit from basic research
		Chapter 6— ``Translational effects of neuro-urology research on clinical practice\'\'; Patient population–specific lower urin ...
		Chapter 7—Effect of androgens and estrogens on bladder/lower urinary tract function
		Chapter 8—Transcriptomic identification of cell types in the lower urinary tract
		Chapter 9—Exploring urinary bladder neural circuitry through calcium imaging
		Chapter 10—The periaqueductal gray and control of bladder function
		Chapter 11—Impact of spinal neuromodulation on spinal neural networks controlling lower urinary tract function
		Chapter 12—Neural control of continence
	Introduction to neuro-urology
		The past and present of neuro-urology research
		Research questions and directions in the neuro-urology field
			Research topic 1: neuroanatomical sites for micturition behavior
			Research topic 2: neural circuits involved in bladder function
			Research topic 3: the functional brain-bladder connection
			Research topic 4: the “brain cause” of common lower urinary tract symptoms
		A quick guide to the “neuroscience toolbox”
			Transgenic animal models: knock-in and knockout (mice)
				Transgenic mice and CRISPR/Cas9 technology
			Cre-lox system and genetic tools
				Neural circuit tracing
			Transcriptomics for identifying the gene expression profile of cells
				Spatially resolving gene expression profiles in intact biological samples
			Recording neural activity
				Fiber photometry during awake CMG
			Cell-specific manipulation of activity
				Optogenetic stimulation or inhibition of neuron activity
				Optogenetics 2.0 and special tools
				Chemogenetics for stimulating or inhibiting neuron activity
				Diphtheria toxin–mediated ablation and tetanus toxin–induced neuronal silencing
				Channelrhodopsin-assisted circuit mapping
			Bladder function readout that can be used with the described tools
				Micturition video thermography void spot assay
				Video cystometry
		Conclusions
	References
I -
Neuroscience in urology research
	2 - Barrington\'s nucleus: a century of progress identifying neurons that control micturition
		Introduction
		The micturition reflex
		Neuroanatomical landscape surrounding Barrington\'s nucleus
			Locus coeruleus
			Pontine central gray
			Pre-locus coeruleus
			Laterodorsal tegmental nucleus
			Mesencephalic nucleus of the trigeminal nerve and fourth ventricle
		Discovery and characterization of the neurons in Barrington\'s nucleus
			Neuroanatomic identification of Bar neurons
			Molecular characterization of Bar neurons
			Additional features of Bar neurons
			Human pontine tegmentum and micturition
		Efferent projections of Bar neurons
		Afferent projections to Bar neurons
		Conclusion
		References
	3 - Voluntary versus reflex micturition control
		Introduction
		Neural circuits involved in reflex micturition control
			Peripheral nervous system
				Parasympathetic pathways
				Sympathetic pathways
				Somatic pathways
				Afferent pathways
			Intraspinal pathways
			Organization of storage reflexes
				Spinal reflex pathways
				Supraspinal pathways
			Organization of voiding reflexes
				Spinobulbospinal reflex pathways
				Brainstem circuitry
					Role of PMC
					Properties of neurons in the PMC
					Role of the PAG
				Spinal micturition pathways
					Developmental changes in micturition pathways
					Reorganization of spinal micturition reflexes due to spinal cord legions
		Neural circuits involved in voluntary micturition control
			Cortical modulation of micturition
				Human imaging studies
				Animal studies
			Subcortical modulation of micturition
				Hypothalamus
				Basal ganglia, substantia nigra pars compacta, and ventral tegmental area
				Cerebellum
		Neurotransmitters in cortical and subcortical controls of micturition
			Glutamate
			Acetylcholine
			GABA and glycine
			Dopamine
			Serotonin (5-hydroxytryptamine)
			Stress-related peptides
		Conclusion
		References
	4 - The bladder as a readout in neuroscience research
		Introduction
		Bladder function as a readout in basic neuroscience studies Electrical stimulation of the brain and measurement of bladder  ...
			Pontine micturition centers
			The periaqueductal gray area
			PPN and rostral pontine areas affecting the micturition reflex
			Cerebellum
			Thalamus and hypothalamus
			Subthalamic nucleus
			Basal ganglia
			Higher (cortical) areas
		Recording of neural activity within the brain during physiological changes in bladder activity
		Optogenetics and pharmacological manipulation of brain circuits with measurement of bladder function
		Bladder function as a readout in clinical neuroscience including developmental, regenerative, and degenerative neuroscience
			Developmental neuroscience
				Spina bifida and tethered cord
				Postnatal emergence of continence in animals and humans
			Degenerative neuroscience
				Parkinson\'s disease
				Normal pressure hydrocephalus
				Multiple system atrophy
			Regenerative neuroscience
				Cauda equina/conus medullaris compression
		The autonomic nervous system and bladder control
			The organization of autonomic pathways innervating the bladder
			The central autonomic network and the bladder
		The bladder as a readout in affective and social neuroscience: understanding the cognition of voiding
		Conclusion
		References
		Further reading
II -
Fundamental and translational neuro-urology research
	5 - How treatment of lower urinary tract symptoms can benefit from basic research
		Introduction
		Afferent bladder pathways
			Location of afferent neurons in lower urinary tract
			Pelvic and pudendal nerve afferents
			Hypogastric nerve afferents
			Spinal interneurons
				Role and properties of lower urinary tract afferent nerves
			Two types of afferent neurons
			Chemical properties of afferent nerves
		Afferent neurons in bladder reflexes
			Role of urothelium
			Neuronal afferents role in LUTS
			Neuronal afferents\' role in painful bladder syndrome and interstitial cystitis
		Conclusion
		References
	6 - “Translational effects of neuro-urology research on clinical practice”; Patient population–specific lower urina ...
		Brain–bladder axis in health
		Nomenclature
		Localization-related symptoms in patients with neurological disease
		Neurological populations with frequent lower urinary tract dysfunction
			Dementia
			Stroke
			Parkinson\'s disease
			Multiple system atrophy
			Multiple sclerosis
			Spinal cord injury
			Spina bifida
			Cauda equina syndrome
		Idiopathic urinary retention: Fowler\'s syndrome and functional urological disorders
		Treatment options for patients with neurological disorders
			Treatment for storage dysfunction
				Behavioral treatment
				Antimuscarinic drugs
				Mirabegron
				Desmopressin
				Alpha-blockers
				Intravesical drug treatment
					Intravesical botulinum toxin
					Intravesical antimuscarinics
					Tibial neuromodulation
					Sacral neuromodulation
			Treatment for voiding dysfunction
				Intermittent self-catheterization
			Surgical options
				Bladder augmentation
				Urinary diversion
				Bladder neck and urethral procedures
				Artificial urinary sphincter
				Urethral sling
			Urinary tract infections
				New investigation and treatment possibilities
					Lower urinary tract classifications and urinary biomarkers
					Deep brain stimulation
					Cannabinoids
					Prophylaxis for UTI bacteriophages
					Early tibial nerve stimulation after SCI
		Conclusion
		References
	7 - Effect of androgens and estrogens on bladder/lower urinary tract function
		Sex differences in bladder histology
		Sex differences in anatomy and physiology
		Sex differences in histology
			Muscle and collagen
		Impact of testosterone and estradiol on smooth muscle physiology
			Smooth muscle
			Nerves
		Testosterone and estradiol in benign bladder diseases
			Lower urinary tract symptoms
			Aging and testosterone and estradiol
		LUTS, testosterone and estradiol, and innervation
			Muscle sensitivity
		Testosterone as a therapy for LUTS
		Stress incontinence
			Aging and T and E2
		Estrogens and innervation
			Estradiol as a therapy
		Overactive bladder
			TRPs in overactive bladder
		Environmental factors that mediate changes in testosterone and estradiol concentrations
			Diet
			Environmental chemical exposure
		Summary and conclusions
		References
		Further reading
	8 - Transcriptomic identification of cell types in the lower urinary tract
		Bulk transcriptional profiling
			Example of bulk RNA sequencing protocol
		Single-cell transcriptional profiling
			Example of tissue digestion protocol
			Overview of single-cell RNA sequencing protocol
			Overview of bioinformatics
			Validation of cell type identification
			Spatial transcriptomics
		Conclusion
		References
III -
Neurobiological tools applied to neuro-urology research
	9 - Exploring urinary bladder neural circuitry through calcium imaging
		Traditional means of recording neuronal function
		Overview of calcium signaling as it applies to neuronal function
			Ca2+ signals versus Na+ signals: what does each say about a neuron?
			From local to global: types of neuronal Ca2+ signals
		Using imaging to measure neuronal function
			Chemical calcium indicators
			Ratiometric calcium indicators
			Intensiometric calcium indicators
			Genetically encoded Ca2+ indicators (GECIs)
		Exploring urinary bladder neural circuitry through calcium imaging
			Epifluorescent/intravital microscopy
			Confocal imaging
			Multiphoton imaging
			Fiber photometry
		Beyond calcium: new frontiers to measure neuronal function
			Membrane potential dyes and genetically encoded voltage indicators
			pH sensitive indicators
			Genetically encoded K+ indicators
			Next-generation microelectrode arrays
		Summary
		References
	10 - The periaqueductal gray and control of bladder function
		Introduction
		Anatomy and neural network of the PAG
			PAG columns
				Functional classification of PAG columns
				PAG projections to the pontine micturition center
				The PAG is a “gate” for the activity of PMC neurons
				Study using c-Fos expression levels in the PAG (activity of bladder control)
		Functional cell populations in the PAG
			Glutamatergic control of micturition
			Dopaminergic control of micturition
			GABAergic control of micturition
			Serotonergic (5-hydroxytryptamine) control of micturition
			In vivo microdialysis study
			Electrical stimulation (deep brain stimulation) of the PAG in humans
			A central switch for micturition
		Human functional magnetic resonance imaging study on the PAG in bladder control as part of functional brain imaging
			Issues in functional brain imaging of micturition reflex
			Working model of lower urinary tract control
		PAG and recent research with lower urinary tract function
			Activation of the PAG during the storage phase
			PAG activation during the voiding phase
			Function of the PAG in patients with lower urinary tract dysfunction
			Animal studies and human research as two wheels of the same cart
		Conclusions and future directions
		References
IV -
Research directions and research opportunities
	11 - Impact of spinal neuromodulation on spinal neural networks controlling lower urinary tract function
		Neurophysiology of the lower urinary tract
			The role of the spinal cord in LUT control
			If an autonomous sacral micturition CPG exists, why does SCI lead to severe LUT dysfunction?
		Current options to alter LUT function after SCI
			Novel neuromodulation techniques to improve LUT function after SCI
			Implantable neuromodulation techniques
				Intraspinal stimulation
				Epidural spinal stimulation
			Noninvasive neuromodulation techniques
				Noninvasive magnetic spinal stimulation
				Transcutaneous electrical spinal cord neuromodulation
				New directions
			Funding
			Author disclosure statement
		References
	12 - Neural control of continence
		Introduction
		Central nervous nystem pathways
			Brain
			Spinal cord
			Link between brain and spinal cord
			Neurotransmitters
		The role of human brain imaging in understanding neural circuits of continence
			Human brain imaging and urge incontinence
				fMRI observations in patients with urge incontinence
			Potential cerebral therapeutic targets for urge incontinence
			Imaging and Fowler\'s syndrome
		Overview of peripheral innervation
		Disruptions in neural control of voiding and associated clinical findings
			Suprapontine lesions
			Bladder outlet obstruction
			Interstitial cystitis and bladder pain syndrome
			Diabetes mellitus and detrusor underactivity
			Developmental changes in neural control of continence
			Aging
			Spinal cord damage
		Future research directions
		References
		Further reading
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
Back Cover