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Physiological Reviews Jan 2021Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is a common chronic pain condition with major impact on quality of life. Examples... (Review)
Review
Neuropathic pain caused by a lesion or disease of the somatosensory nervous system is a common chronic pain condition with major impact on quality of life. Examples include trigeminal neuralgia, painful polyneuropathy, postherpetic neuralgia, and central poststroke pain. Most patients complain of an ongoing or intermittent spontaneous pain of, for example, burning, pricking, squeezing quality, which may be accompanied by evoked pain, particular to light touch and cold. Ectopic activity in, for example, nerve-end neuroma, compressed nerves or nerve roots, dorsal root ganglia, and the thalamus may in different conditions underlie the spontaneous pain. Evoked pain may spread to neighboring areas, and the underlying pathophysiology involves peripheral and central sensitization. Maladaptive structural changes and a number of cell-cell interactions and molecular signaling underlie the sensitization of nociceptive pathways. These include alteration in ion channels, activation of immune cells, glial-derived mediators, and epigenetic regulation. The major classes of therapeutics include drugs acting on αδ subunits of calcium channels, sodium channels, and descending modulatory inhibitory pathways.
Topics: Animals; Central Nervous System; Humans; Nerve Fibers; Neuralgia; Peripheral Nerves; Peripheral Nervous System
PubMed: 32584191
DOI: 10.1152/physrev.00045.2019 -
Cell Jan 2022Neurons of the mammalian central nervous system fail to regenerate. Substantial progress has been made toward identifying the cellular and molecular mechanisms that... (Review)
Review
Neurons of the mammalian central nervous system fail to regenerate. Substantial progress has been made toward identifying the cellular and molecular mechanisms that underlie regenerative failure and how altering those pathways can promote cell survival and/or axon regeneration. Here, we summarize those findings while comparing the regenerative process in the central versus the peripheral nervous system. We also highlight studies that advance our understanding of the mechanisms underlying neural degeneration in response to injury, as many of these mechanisms represent primary targets for restoring functional neural circuits.
Topics: Animals; Axons; Central Nervous System; Humans; Nerve Regeneration; Neurons; Peripheral Nervous System; Signal Transduction
PubMed: 34995518
DOI: 10.1016/j.cell.2021.10.029 -
Nature Reviews. Neuroscience Nov 2021The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or... (Review)
Review
The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or regulation of body temperature. Sympathetic regulation of bodily functions requires the establishment and refinement of anatomically and functionally precise connections between postganglionic sympathetic neurons and peripheral organs distributed widely throughout the body. Mechanistic studies of key events in the formation of postganglionic sympathetic neurons during embryonic and early postnatal life, including axon growth, target innervation, neuron survival, and dendrite growth and synapse formation, have advanced the understanding of how neuronal development is shaped by interactions with peripheral tissues and organs. Recent progress has also been made in identifying how the cellular and molecular diversity of sympathetic neurons is established to meet the functional demands of peripheral organs. In this Review, we summarize current knowledge of signalling pathways underlying the development of the sympathetic nervous system. These findings have implications for unravelling the contribution of sympathetic dysfunction stemming, in part, from developmental perturbations to the pathophysiology of peripheral neuropathies and cardiovascular and metabolic disorders.
Topics: Animals; Axons; Dendrites; Humans; Neuronal Plasticity; Neurons; Peripheral Nervous System Diseases; Sympathetic Nervous System
PubMed: 34599308
DOI: 10.1038/s41583-021-00523-y -
Development (Cambridge, England) May 2023The peripheral nervous system (PNS) represents a highly heterogeneous entity with a broad range of functions, ranging from providing communication between the brain and...
The peripheral nervous system (PNS) represents a highly heterogeneous entity with a broad range of functions, ranging from providing communication between the brain and the body to controlling development, stem cell niches and regenerative processes. According to the structure and function, the PNS can be subdivided into sensory, motor (i.e. the nerve fibers of motor neurons), autonomic and enteric domains. Different types of neurons correspond to these domains and recent progress in single-cell transcriptomics has enabled the discovery of new neuronal subtypes and improved the previous cell-type classifications. The developmental mechanisms generating the domains of the PNS reveal a range of embryonic strategies, including a variety of cell sources, such as migratory neural crest cells, placodal neurogenic cells and even recruited nerve-associated Schwann cell precursors. In this article, we discuss the diversity of roles played by the PNS in our body, as well as the origin, wiring and heterogeneity of every domain. We place a special focus on the most recent discoveries and concepts in PNS research, and provide an outlook of future perspectives and controversies in the field.
Topics: Peripheral Nervous System; Neurogenesis; Neural Crest; Schwann Cells; Motor Neurons
PubMed: 37170957
DOI: 10.1242/dev.201164 -
Annual Review of Neuroscience Jul 2022Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously... (Review)
Review
Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously appreciated. Moreover, technological advances have enabled the identification of the molecular mediators and receptors that enable the interaction between these two complex systems and provide new insights on the role of neuroimmune crosstalk in organismal physiology. Most neuroimmune interactions occur at discrete anatomical locations in which neurons and immune cells colocalize. Here, we describe the interactions of the different branches of the peripheral nervous system with immune cells in various organs, including the skin, intestine, lung, and adipose tissue. We highlight how neuroimmune crosstalk orchestrates physiological processes such as host defense, tissue repair, metabolism, and thermogenesis. Unraveling these intricate relationships is invaluable to explore the therapeutic potential of neuroimmune interactions.
Topics: Immune System; Neuroimmunomodulation; Peripheral Nervous System
PubMed: 35363534
DOI: 10.1146/annurev-neuro-111020-105359 -
Nature May 2022Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes. As plaques lack innervation, the effects of neuronal...
Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes. As plaques lack innervation, the effects of neuronal control on atherosclerosis remain unclear. However, the immune system responds to plaques by forming leukocyte infiltrates in the outer connective tissue coat of arteries (the adventitia). Here, because the peripheral nervous system uses the adventitia as its principal conduit to reach distant targets, we postulated that the peripheral nervous system may directly interact with diseased arteries. Unexpectedly, widespread neuroimmune cardiovascular interfaces (NICIs) arose in mouse and human atherosclerosis-diseased adventitia segments showed expanded axon networks, including growth cones at axon endings near immune cells and media smooth muscle cells. Mouse NICIs established a structural artery-brain circuit (ABC): abdominal adventitia nociceptive afferents entered the central nervous system through spinal cord T-T dorsal root ganglia and were traced to higher brain regions, including the parabrachial and central amygdala neurons; and sympathetic efferent neurons projected from medullary and hypothalamic neurons to the adventitia through spinal intermediolateral neurons and both coeliac and sympathetic chain ganglia. Moreover, ABC peripheral nervous system components were activated: splenic sympathetic and coeliac vagus nerve activities increased in parallel to disease progression, whereas coeliac ganglionectomy led to the disintegration of adventitial NICIs, reduced disease progression and enhanced plaque stability. Thus, the peripheral nervous system uses NICIs to assemble a structural ABC, and therapeutic intervention in the ABC attenuates atherosclerosis.
Topics: Animals; Atherosclerosis; Disease Progression; Ganglia, Spinal; Ganglia, Sympathetic; Mice; Neurons; Plaque, Atherosclerotic
PubMed: 35477759
DOI: 10.1038/s41586-022-04673-6 -
Biochimica Et Biophysica Acta. Reviews... Nov 2022Recent studies have shown that peripheral nerves play an important role in the progression of breast cancer. Breast cancer cells (BCCs) promote local peripheral nerve... (Review)
Review
Recent studies have shown that peripheral nerves play an important role in the progression of breast cancer. Breast cancer cells (BCCs) promote local peripheral nerve growth and branching by secreting neuroactive molecules, including neurotrophins and axon guidance molecules (AGMs). Sympathetic nerves promote breast cancer progression, while parasympathetic and sensory nerves mainly have anti-tumor effects in the progression of breast cancer. Specifically, peripheral nerves can influence the progression of breast cancer by secreting neurotransmitters not only directly binding to the corresponding receptors of BCCs, but also indirectly acting on immune cells to modulate anti-tumor immunity. In this review, we summarize the crosstalk between breast cancer and peripheral nerves and the roles of important neuroactive molecules in the progression of breast cancer. In addition, we summarize indicators, including nerve fiber density and perineural invasion (PNI), that may help determine the prognosis of breast cancer based on current research results, as well as potential therapeutic approaches, such as β-blockers and retroviral-mediated genetic neuroengineering techniques, that may enhance the prognosis of breast cancer. In addition, we propose suggestions for future research priorities based on a current lack of knowledge in this area.
Topics: Humans; Female; Neoplasm Invasiveness; Breast Neoplasms; Axon Guidance; Peripheral Nervous System
PubMed: 36283598
DOI: 10.1016/j.bbcan.2022.188828 -
Annual Review of Cell and Developmental... Oct 2019Molecular cross talk between the nervous and vascular systems is necessary to maintain the correct coupling of organ structure and function. Molecular pathways shared by... (Review)
Review
Molecular cross talk between the nervous and vascular systems is necessary to maintain the correct coupling of organ structure and function. Molecular pathways shared by both systems are emerging as major players in the communication of the neuronal compartment with the endothelium. Here we review different aspects of this cross talk and how vessels influence the development and homeostasis of the nervous system. Beyond the classical role of the vasculature as a conduit to deliver oxygen and metabolites needed for the energy-demanding neuronal compartment, vessels emerge as powerful signaling systems that control and instruct a variety of cellular processes during the development of neurons and glia, such as migration, differentiation, and structural connectivity. Moreover, a broad spectrum of mild to severe vascular dysfunctions occur in various pathologies of the nervous system, suggesting that mild structural and functional changes at the neurovascular interface may underlie cognitive decline in many of these pathological conditions.
Topics: Animals; Blood Vessels; Cell Differentiation; Cell Movement; Central Nervous System; Homeostasis; Humans; Nervous System Diseases; Neuroglia; Neurons; Neurovascular Coupling; Peripheral Nervous System
PubMed: 31590587
DOI: 10.1146/annurev-cellbio-100818-125142 -
Annual Review of Neuroscience Jul 2019Maturation of neuronal circuits requires selective elimination of synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is... (Review)
Review
Maturation of neuronal circuits requires selective elimination of synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is increasingly recognized that glial cells also play a critical role. Without proper functioning of these cells, the number, morphology, and function of synaptic contacts are profoundly altered, resulting in abnormal connectivity and behavioral abnormalities. In addition to their role in synaptic refinement, glial cells have also been implicated in pathological synapse loss and dysfunction following injury or nervous system degeneration in adults. Although mechanisms regulating glia-mediated synaptic elimination are still being uncovered, it is clear this complex process involves many cues that promote and inhibit the removal of specific synaptic connections. Gaining a greater understanding of these signals and the contribution of different cell types will not only provide insight into this critical biological event but also be instrumental in advancing knowledge of brain development and neural disease.
Topics: Animals; Astrocytes; Biological Evolution; Central Nervous System; Cues; Exosomes; Humans; Invertebrates; Microglia; Morphogenesis; Myelin Sheath; Nerve Degeneration; Nervous System Diseases; Neuroglia; Neuromuscular Junction; Neurons; Peripheral Nervous System; Synapses
PubMed: 31283900
DOI: 10.1146/annurev-neuro-070918-050306 -
CNS Neuroscience & Therapeutics Jan 2020Neurotropic B vitamins play crucial roles as coenzymes and beyond in the nervous system. Particularly vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin)... (Review)
Review
BACKGROUND
Neurotropic B vitamins play crucial roles as coenzymes and beyond in the nervous system. Particularly vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) contribute essentially to the maintenance of a healthy nervous system. Their importance is highlighted by many neurological diseases related to deficiencies in one or more of these vitamins, but they can improve certain neurological conditions even without a (proven) deficiency.
AIM
This review focuses on the most important biochemical mechanisms, how they are linked with neurological functions and what deficits arise from malfunctioning of these pathways.
DISCUSSION
We discussed the main role of B Vitamins on several functions in the peripheral and central nervous system (PNS and CNS) including cellular energetic processes, antioxidative and neuroprotective effects, and both myelin and neurotransmitter synthesis. We also provide an overview of possible biochemical synergies between thiamine, pyridoxine, and cobalamin and discuss by which major roles each of them may contribute to the synergy and how these functions are inter-related and complement each other.
CONCLUSION
Taking into account the current knowledge on the neurotropic vitamins B1, B6, and B12, we conclude that a biochemical synergy becomes apparent in many different pathways in the nervous system, particularly in the PNS as exemplified by their combined use in the treatment of peripheral neuropathy.
Topics: Animals; Central Nervous System; Humans; Nervous System Diseases; Nervous System Physiological Phenomena; Peripheral Nervous System; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex
PubMed: 31490017
DOI: 10.1111/cns.13207