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Special Issue "Molecular Mechanisms of Neural Circuit Development and Regeneration"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 January 2021).

Special Issue Editors

Dr. Lies De Groef
E-Mail Website
Guest Editor
Neural Circuit Development and Regeneration Research Group, Department of Biology, University of Leuven, Leuven, Belgium
Interests: neurodegeneration; neuroinflammation; retina; optic nerve; mouse; protein aggregation; Parkinson’s disease; extracellular vesicles; intercellular transport and communication
Special Issues and Collections in MDPI journals
Prof. Dr. Lieve Moons
E-Mail Website
Guest Editor
Neural Circuit Development and Regeneration Research Group, Department of Biology, University of Leuven, Leuven, Belgium
Interests: neurodegeneration; axonal regeneration; neuroinflammation; retina; optic nerve; mouse; teleost fish; mitochondria; intraneuronal transport and communication
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The human brain has one hundred billion neurons, each neuron connected to ten thousand other neurons. Understanding how these neural circuits are formed and what is needed for them to be repaired is one of the biggest challenges in modern science. Studies in different animal models have helped to unravel the principles of neural circuit formation yet have also pointed out striking differences in the regenerative capacity of the central nervous system (CNS) among species. Further insights into the gene networks, molecular players, and (sub)cellular entities responsible for neural circuit formation are still urgently needed and may propel the search for neuroprotective and -reparative strategies to treat neurodevelopmental and neurodegenerative conditions.

An intriguing question with respect to neural circuit formation is how this process is being orchestrated in the developing CNS, and whether this developmental program can be used to regenerate adult neural circuits. We especially encourage submissions that address the common or differential molecular and cellular mechanisms involved in neurodevelopment and -regeneration, as well as other comparative research focusing on, e.g., animal model organisms with different regenerative capacities, CNS versus peripheral nervous system repair.

The Special Issue is open to original papers, reviews, and other forms of scientific communication that increase our fundamental understanding of neural circuit development and regeneration.

Dr. Lies De Groef
Prof. Dr. Lieve Moons
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Axonal development/regeneration
  • Axonal branching
  • Neurogenesis
  • Stem cells
  • Neuroprotection
  • Neural circuit formation
  • Neural circuit recovery
  • Regenerative potential
  • Central nervous system
  • Peripheral nervous system
  • Comparative research
  • Molecular mechanisms
  • Cellular mechanisms

Published Papers (15 papers)

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Editorial

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Editorial
Molecular Mechanisms of Neural Circuit Development and Regeneration
Int. J. Mol. Sci. 2021, 22(9), 4593; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094593 - 27 Apr 2021
Viewed by 293
Abstract
The human brain contains 86 billion neurons [...] Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)

Research

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Article
Investigating Primary Cilia during Peripheral Nervous System Formation
Int. J. Mol. Sci. 2021, 22(6), 3176; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063176 - 20 Mar 2021
Cited by 1 | Viewed by 710
Abstract
The primary cilium plays a pivotal role during the embryonic development of vertebrates. It acts as a somatic signaling hub for specific pathways, such as Sonic Hedgehog signaling. In humans, mutations in genes that cause dysregulation of ciliogenesis or ciliary function lead to [...] Read more.
The primary cilium plays a pivotal role during the embryonic development of vertebrates. It acts as a somatic signaling hub for specific pathways, such as Sonic Hedgehog signaling. In humans, mutations in genes that cause dysregulation of ciliogenesis or ciliary function lead to severe developmental disorders called ciliopathies. Beyond its role in early morphogenesis, growing evidence points towards an essential function of the primary cilium in neural circuit formation in the central nervous system. However, very little is known about a potential role in the formation of the peripheral nervous system. Here, we investigate the presence of the primary cilium in neural crest cells and their derivatives in the trunk of developing chicken embryos in vivo. We found that neural crest cells, sensory neurons, and boundary cap cells all bear a primary cilium during key stages of early peripheral nervous system formation. Moreover, we describe differences in the ciliation of neuronal cultures of different populations from the peripheral and central nervous systems. Our results offer a framework for further in vivo and in vitro investigations on specific roles that the primary cilium might play during peripheral nervous system formation. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Article
Differential Distribution of RBPMS in Pig, Rat, and Human Retina after Damage
Int. J. Mol. Sci. 2020, 21(23), 9330; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239330 - 07 Dec 2020
Cited by 4 | Viewed by 593
Abstract
RNA binding protein with multiple splicing (RBPMS) is expressed exclusively in retinal ganglion cells (RGCs) in the retina and can label all RGCs in normal retinas of mice, rats, guinea pigs, rabbits, cats, and monkeys, but its function in these cells is not [...] Read more.
RNA binding protein with multiple splicing (RBPMS) is expressed exclusively in retinal ganglion cells (RGCs) in the retina and can label all RGCs in normal retinas of mice, rats, guinea pigs, rabbits, cats, and monkeys, but its function in these cells is not known. As a result of the limited knowledge regarding RBPMS, we analyzed the expression of RBPMS in the retina of different mammalian species (humans, pigs, and rats), in various stages of development (neonatal and adult) and with different levels of injury (control, hypoxia, and organotypic culture or explants). In control conditions, RBPMS was localized in the RGCs somas in the ganglion cell layer, whereas in hypoxic conditions, it was localized in the RGCs dendrites in the inner plexiform layer. Such differential distributions of RBPMS occurred in all analyzed species, and in adult and neonatal retinas. Furthermore, we demonstrate RBPMS localization in the degenerating RGCs axons in the nerve fiber layer of retinal explants. This is the first evidence regarding the possible transport of RBPMS in response to physiological damage in a mammalian retina. Therefore, RBPMS should be further investigated in relation to its role in axonal and dendritic degeneration. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Article
Calsequestrin Deletion Facilitates Hippocampal Synaptic Plasticity and Spatial Learning in Post-Natal Development
Int. J. Mol. Sci. 2020, 21(15), 5473; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155473 - 31 Jul 2020
Cited by 1 | Viewed by 733
Abstract
Experimental evidence highlights the involvement of the endoplasmic reticulum (ER)-mediated Ca2+ signals in modulating synaptic plasticity and spatial memory formation in the hippocampus. Ca2+ release from the ER mainly occurs through two classes of Ca2+ channels, inositol 1,4,5-trisphosphate receptors (InsP3Rs) [...] Read more.
Experimental evidence highlights the involvement of the endoplasmic reticulum (ER)-mediated Ca2+ signals in modulating synaptic plasticity and spatial memory formation in the hippocampus. Ca2+ release from the ER mainly occurs through two classes of Ca2+ channels, inositol 1,4,5-trisphosphate receptors (InsP3Rs) and ryanodine receptors (RyRs). Calsequestrin (CASQ) and calreticulin (CR) are the most abundant Ca2+-binding proteins allowing ER Ca2+ storage. The hippocampus is one of the brain regions expressing CASQ, but its role in neuronal activity, plasticity, and the learning processes is poorly investigated. Here, we used knockout mice lacking both CASQ type-1 and type-2 isoforms (double (d)CASQ-null mice) to: a) evaluate in adulthood the neuronal electrophysiological properties and synaptic plasticity in the hippocampal Cornu Ammonis 1 (CA1) field and b) study the performance of knockout mice in spatial learning tasks. The ablation of CASQ increased the CA1 neuron excitability and improved the long-term potentiation (LTP) maintenance. Consistently, (d)CASQ-null mice performed significantly better than controls in the Morris Water Maze task, needing a shorter time to develop a spatial preference for the goal. The Ca2+ handling analysis in CA1 pyramidal cells showed a decrement of Ca2+ transient amplitude in (d)CASQ-null mouse neurons, which is consistent with a decrease in afterhyperpolarization improving LTP. Altogether, our findings suggest that CASQ deletion affects activity-dependent ER Ca2+ release, thus facilitating synaptic plasticity and spatial learning in post-natal development. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Article
Tau Gene Deletion Does Not Influence Axonal Regeneration and Retinal Neuron Survival in the Injured Mouse Visual System
Int. J. Mol. Sci. 2020, 21(11), 4100; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21114100 - 08 Jun 2020
Cited by 1 | Viewed by 871
Abstract
In the present study, we hypothesized that the microtubule-associated protein Tau may influence retinal neuron survival and axonal regeneration after optic nerve injury. To test this hypothesis, the density of retinal ganglion cells was evaluated by immunostaining retinal flat-mounts for RNA-binding protein with [...] Read more.
In the present study, we hypothesized that the microtubule-associated protein Tau may influence retinal neuron survival and axonal regeneration after optic nerve injury. To test this hypothesis, the density of retinal ganglion cells was evaluated by immunostaining retinal flat-mounts for RNA-binding protein with multiple splicing (RBPMS) two weeks after optic nerve micro-crush lesion in Tau-deprived (Tau knock-out (KO)) and wild-type (WT) mice. Axon growth was determined on longitudinal sections of optic nerves after anterograde tracing. Our results showed that the number of surviving retinal ganglion cells and growing axons did not significantly vary between WT and Tau KO animals. Moreover, sustained activation of the neuronal growth program with ciliary neurotrophic factor (CNTF) resulted in a similar increase in surviving neurons and in growing axons in WT and Tau KO mice. Taken together, our data suggest that Tau does not influence axonal regeneration or neuronal survival. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Article
GABAergic Input Affects Intracellular Calcium Levels in Developing Granule Cells of Adult Rat Hippocampus
Int. J. Mol. Sci. 2020, 21(5), 1715; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051715 - 03 Mar 2020
Cited by 4 | Viewed by 902
Abstract
In the dentate gyrus (DG) of the mammalian hippocampus, granule neurons are generated from neural stem cells (NSCs) throughout the life span and are integrated into the hippocampal network. Adult DG neurogenesis is regulated by multiple intrinsic and extrinsic factors that control NSC [...] Read more.
In the dentate gyrus (DG) of the mammalian hippocampus, granule neurons are generated from neural stem cells (NSCs) throughout the life span and are integrated into the hippocampal network. Adult DG neurogenesis is regulated by multiple intrinsic and extrinsic factors that control NSC proliferation, maintenance, and differentiation into mature neurons. γ-Aminobutyric acid (GABA), released by local interneurons, regulates the development of neurons born in adulthood by activating extrasynaptic and synaptic GABAA receptors. In the present work, patch-clamp and calcium imaging techniques were used to record very immature granule cells of adult rat dentate gyrus for investigating the actual role of GABAA receptor activation in intracellular calcium level regulation at an early stage of maturation. Our findings highlight a novel molecular and electrophysiological mechanism, involving calcium-activated potassium channels (BK) and T-type voltage-dependent calcium channels, through which GABA fine-tunes intracellular calcium homeostasis in rat adult-born granule neurons early during their maturation. This mechanism might be instrumental in promoting newborn cell survival. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Article
DRG2 Deficient Mice Exhibit Impaired Motor Behaviors with Reduced Striatal Dopamine Release
Int. J. Mol. Sci. 2020, 21(1), 60; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010060 - 20 Dec 2019
Cited by 3 | Viewed by 1275
Abstract
Developmentally regulated GTP-binding protein 2 (DRG2) was first identified in the central nervous system of mice. However, the physiological function of DRG2 in the brain remains largely unknown. Here, we demonstrated that knocking out DRG2 impairs the function of dopamine neurons in mice. [...] Read more.
Developmentally regulated GTP-binding protein 2 (DRG2) was first identified in the central nervous system of mice. However, the physiological function of DRG2 in the brain remains largely unknown. Here, we demonstrated that knocking out DRG2 impairs the function of dopamine neurons in mice. DRG2 was strongly expressed in the neurons of the dopaminergic system such as those in the striatum (Str), ventral tegmental area (VTA), and substantia nigra (SN), and on neuronal cell bodies in high-density regions such as the hippocampus (HIP), cerebellum, and cerebral cortex in the mouse brain. DRG2 knockout (KO) mice displayed defects in motor function in motor coordination and rotarod tests and increased anxiety. However, unexpectedly, DRG2 depletion did not affect the dopamine (DA) neuron population in the SN, Str, or VTA region or dopamine synthesis in the Str region. We further demonstrated that dopamine release was significantly diminished in the Str region of DRG2 KO mice and that treatment of DRG2 KO mice with l-3,4-dihydroxyphenylalanine (L-DOPA), a dopamine precursor, rescued the behavioral motor deficiency in DRG2 KO mice as observed with the rotarod test. This is the first report to identify DRG2 as a key regulator of dopamine release from dopamine neurons in the mouse brain. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Review

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Review
Neural Circuitry–Neurogenesis Coupling Model of Depression
Int. J. Mol. Sci. 2021, 22(5), 2468; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052468 - 28 Feb 2021
Cited by 2 | Viewed by 553
Abstract
Depression is characterized by the disruption of both neural circuitry and neurogenesis. Defects in hippocampal activity and volume, indicative of reduced neurogenesis, are associated with depression-related behaviors in both humans and animals. Neurogenesis in adulthood is considered an activity-dependent process; therefore, hippocampal neurogenesis [...] Read more.
Depression is characterized by the disruption of both neural circuitry and neurogenesis. Defects in hippocampal activity and volume, indicative of reduced neurogenesis, are associated with depression-related behaviors in both humans and animals. Neurogenesis in adulthood is considered an activity-dependent process; therefore, hippocampal neurogenesis defects in depression can be a result of defective neural circuitry activity. However, the mechanistic understanding of how defective neural circuitry can induce neurogenesis defects in depression remains unclear. This review highlights the current findings supporting the neural circuitry-regulated neurogenesis, especially focusing on hippocampal neurogenesis regulated by the entorhinal cortex, with regard to memory, pattern separation, and mood. Taken together, these findings may pave the way for future progress in neural circuitry–neurogenesis coupling studies of depression. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Review
In Search of Molecular Markers for Cerebellar Neurons
Int. J. Mol. Sci. 2021, 22(4), 1850; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041850 - 12 Feb 2021
Cited by 2 | Viewed by 646
Abstract
The cerebellum, the region of the brain primarily responsible for motor coordination and balance, also contributes to non-motor functions, such as cognition, speech, and language comprehension. Maldevelopment and dysfunction of the cerebellum lead to cerebellar ataxia and may even be associated with autism, [...] Read more.
The cerebellum, the region of the brain primarily responsible for motor coordination and balance, also contributes to non-motor functions, such as cognition, speech, and language comprehension. Maldevelopment and dysfunction of the cerebellum lead to cerebellar ataxia and may even be associated with autism, depression, and cognitive deficits. Hence, normal development of the cerebellum and its neuronal circuitry is critical for the cerebellum to function properly. Although nine major types of cerebellar neurons have been identified in the cerebellar cortex to date, the exact functions of each type are not fully understood due to a lack of cell-specific markers in neurons that renders cell-specific labeling and functional study by genetic manipulation unfeasible. The availability of cell-specific markers is thus vital for understanding the role of each neuronal type in the cerebellum and for elucidating the interactions between cell types within both the developing and mature cerebellum. This review discusses various technical approaches and recent progress in the search for cell-specific markers for cerebellar neurons. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Review
Axonal Organelles as Molecular Platforms for Axon Growth and Regeneration after Injury
Int. J. Mol. Sci. 2021, 22(4), 1798; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041798 - 11 Feb 2021
Cited by 2 | Viewed by 1069
Abstract
Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that [...] Read more.
Investigating the molecular mechanisms governing developmental axon growth has been a useful approach for identifying new strategies for boosting axon regeneration after injury, with the goal of treating debilitating conditions such as spinal cord injury and vision loss. The picture emerging is that various axonal organelles are important centers for organizing the molecular mechanisms and machinery required for growth cone development and axon extension, and these have recently been targeted to stimulate robust regeneration in the injured adult central nervous system (CNS). This review summarizes recent literature highlighting a central role for organelles such as recycling endosomes, the endoplasmic reticulum, mitochondria, lysosomes, autophagosomes and the proteasome in developmental axon growth, and describes how these organelles can be targeted to promote axon regeneration after injury to the adult CNS. This review also examines the connections between these organelles in developing and regenerating axons, and finally discusses the molecular mechanisms within the axon that are required for successful axon growth. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Review
In the Right Place at the Right Time: miRNAs as Key Regulators in Developing Axons
Int. J. Mol. Sci. 2020, 21(22), 8726; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228726 - 18 Nov 2020
Cited by 1 | Viewed by 778
Abstract
During neuronal circuit formation, axons progressively develop into a presynaptic compartment aided by extracellular signals. Axons display a remarkably high degree of autonomy supported in part by a local translation machinery that permits the subcellular production of proteins required for their development. Here, [...] Read more.
During neuronal circuit formation, axons progressively develop into a presynaptic compartment aided by extracellular signals. Axons display a remarkably high degree of autonomy supported in part by a local translation machinery that permits the subcellular production of proteins required for their development. Here, we review the latest findings showing that microRNAs (miRNAs) are critical regulators of this machinery, orchestrating the spatiotemporal regulation of local translation in response to cues. We first survey the current efforts toward unraveling the axonal miRNA repertoire through miRNA profiling, and we reveal the presence of a putative axonal miRNA signature. We also provide an overview of the molecular underpinnings of miRNA action. Our review of the available experimental evidence delineates two broad paradigms: cue-induced relief of miRNA-mediated inhibition, leading to bursts of protein translation, and cue-induced miRNA activation, which results in reduced protein production. Overall, this review highlights how a decade of intense investigation has led to a new appreciation of miRNAs as key elements of the local translation regulatory network controlling axon development. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Review
Molecular Mechanisms of Central Nervous System Axonal Regeneration and Remyelination: A Review
Int. J. Mol. Sci. 2020, 21(21), 8116; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218116 - 30 Oct 2020
Cited by 2 | Viewed by 773
Abstract
Central nervous system (CNS) injury, including stroke, spinal cord injury, and traumatic brain injury, causes severe neurological symptoms such as sensory and motor deficits. Currently, there is no effective therapeutic method to restore neurological function because the adult CNS has limited capacity to [...] Read more.
Central nervous system (CNS) injury, including stroke, spinal cord injury, and traumatic brain injury, causes severe neurological symptoms such as sensory and motor deficits. Currently, there is no effective therapeutic method to restore neurological function because the adult CNS has limited capacity to regenerate after injury. Many efforts have been made to understand the molecular and cellular mechanisms underlying CNS regeneration and to establish novel therapeutic methods based on these mechanisms, with a variety of strategies including cell transplantation, modulation of cell intrinsic molecular mechanisms, and therapeutic targeting of the pathological nature of the extracellular environment in CNS injury. In this review, we will focus on the mechanisms that regulate CNS regeneration, highlighting the history, recent efforts, and questions left unanswered in this field. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Review
Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link
Int. J. Mol. Sci. 2020, 21(16), 5850; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165850 - 14 Aug 2020
Cited by 8 | Viewed by 1031
Abstract
Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss [...] Read more.
Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss how these gestational factors affect placental and fetal brain 5-HT levels, leading to changes in brain structure and function and behavior. We conclude that gestational factors are able to interact and thereby amplify or counteract each other’s impact on the fetal 5-HT-ergic system. We, therefore, argue that beyond the understanding of how single gestational factors affect 5-HT-ergic brain development and behavior in offspring, it is critical to elucidate the consequences of interacting factors. Moreover, we describe how each gestational factor is able to alter the 5-HT-ergic influence on the thalamocortical- and prefrontal-limbic circuitry and the hypothalamo-pituitary-adrenocortical-axis. These alterations have been associated with risks to develop attention deficit hyperactivity disorder, autism spectrum disorders, depression, and/or anxiety. Consequently, the manipulation of gestational factors may be used to combat pregnancy-related risks for neuropsychiatric disorders. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Review
Trans-Axonal Signaling in Neural Circuit Wiring
Int. J. Mol. Sci. 2020, 21(14), 5170; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145170 - 21 Jul 2020
Cited by 2 | Viewed by 1008
Abstract
The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon–environment and axon–target interactions have long been known as essential for circuit formation, communication between axons themselves has [...] Read more.
The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon–environment and axon–target interactions have long been known as essential for circuit formation, communication between axons themselves has only more recently emerged as another crucial mechanism. Trans-axonal signaling governs many axonal behaviors, including fasciculation for proper guidance to targets, defasciculation for pathfinding at important choice points, repulsion along and within tracts for pre-target sorting and target selection, repulsion at the target for precise synaptic connectivity, and potentially selective degeneration for circuit refinement. This review outlines the recent advances in identifying the molecular mechanisms of trans-axonal signaling and discusses the role of axon–axon interactions during the different steps of neural circuit formation. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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Review
Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System
Int. J. Mol. Sci. 2020, 21(7), 2273; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072273 - 25 Mar 2020
Cited by 2 | Viewed by 1501
Abstract
Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological [...] Read more.
Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological signal transduction effector in CNS regeneration by stimulating neuronal intrinsic and extrinsic mechanisms as well as mitochondrial biogenesis. CO may give directions by which the injured neurovascular system switches into regeneration mode by stimulating endogenous neural stem cells and endothelial cells to produce neurons and vessels capable of replacing injured neurons and vessels in the CNS. The present review discusses the regenerative potential of CO in acute and chronic neuroinflammatory diseases of the CNS, such as stroke, traumatic brain injury, multiple sclerosis and Alzheimer’s disease and the role of signaling pathways and neurotrophic factors. CO-mediated facilitation of cellular communications may boost regeneration, consequently forming functional adult neural circuits in CNS injury. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Neural Circuit Development and Regeneration)
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