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Cell Reports Apr 2024Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are...
Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBN Calca neurons from releasing neurotransmitters, we demonstrate that activation of Calca neurons is necessary for the manifestation and maintenance of chronic pain. Additionally, by directly stimulating Calca neurons, we demonstrate that Calca neuron activity is sufficient to drive nociplasticity. Aversive stimuli of multiple sensory modalities, such as exposure to nitroglycerin, cisplatin, or lithium chloride, can drive nociplasticity in a Calca-neuron-dependent manner. Aversive events drive nociplasticity in Calca neurons in the form of increased activity and excitability; however, neuroplasticity also appears to occur in downstream circuitry.
Topics: Animals; Parabrachial Nucleus; Neurons; Mice; Neuronal Plasticity; Male; Mice, Inbred C57BL
PubMed: 38583149
DOI: 10.1016/j.celrep.2024.114057 -
International Journal of Molecular... Jan 2024Serotonin or 5-hydroxytryptamine (5-HT) is a ubiquitous neuro-modulator-transmitter that acts in the central nervous system, playing a major role in the control of... (Review)
Review
Serotonin or 5-hydroxytryptamine (5-HT) is a ubiquitous neuro-modulator-transmitter that acts in the central nervous system, playing a major role in the control of breathing and other physiological functions. The midbrain, pons, and medulla regions contain several serotonergic nuclei with distinct physiological roles, including regulating the hypercapnic ventilatory response, upper airway patency, and sleep-wake states. Obesity is a major risk factor in the development of sleep-disordered breathing (SDB), such as obstructive sleep apnea (OSA), recurrent closure of the upper airway during sleep, and obesity hypoventilation syndrome (OHS), a condition characterized by daytime hypercapnia and hypoventilation during sleep. Approximately 936 million adults have OSA, and 32 million have OHS worldwide. 5-HT acts on 5-HT receptor subtypes that modulate neural control of breathing and upper airway patency. This article reviews the role of 5-HT in SDB and the current advances in 5-HT-targeted treatments for SDB.
Topics: Humans; Serotonin; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Obesity; Sleep; Hypercapnia
PubMed: 38338762
DOI: 10.3390/ijms25031483 -
Proceedings of the National Academy of... Aug 2023The locus coeruleus (LC) is a small nucleus in the pons from which ascending and descending projections innervate major parts of the central nervous system. Its major...
The locus coeruleus (LC) is a small nucleus in the pons from which ascending and descending projections innervate major parts of the central nervous system. Its major transmitter is norepinephrine (NE). This system is evolutionarily conserved, including in humans, and its functions are associated with wakefulness and related to disorders, such as depression. Here, we performed single-cell ribonucleic acid-sequencing (RNA-seq) to subdivide neurons in the LC (24 clusters in total) into 3 NE, 17 glutamate, and 5 γ-aminobutyric acid (GABA) subtypes, and to chart their neuropeptide, cotransmitter, and receptor profiles. We found that NE neurons expressed at least 19 neuropeptide transcripts, notably galanin () but not , and >30 neuropeptide receptors. Among the galanin receptors, was expressed in ~19% of NE neurons, as was also confirmed by in situ hybridization. Unexpectedly, was highly expressed in GABA neurons surrounding the NE ensemble. Patch-clamp electrophysiology and cell-type-specific Ca-imaging using GCaMP6s revealed that a GalR1 agonist inhibits up to ~35% of NE neurons. This effect is direct and does not rely on feed-forward GABA inhibition. Our results define a role for the galanin system in NE functions, and a conceptual framework for the action of many other peptides and their receptors.
Topics: Humans; Animals; Mice; Galanin; Locus Coeruleus; Neurons; Peptide Hormones; Glutamic Acid; Norepinephrine
PubMed: 37487094
DOI: 10.1073/pnas.2222095120 -
Research Square Nov 2023The brainstem is a fundamental component of the central nervous system yet it is typically excluded from human brain mapping efforts, precluding a complete...
The brainstem is a fundamental component of the central nervous system yet it is typically excluded from human brain mapping efforts, precluding a complete understanding of how the brainstem influences cortical function. Here we use high-resolution 7 Tesla fMRI to derive a functional connectome encompassing cortex as well as 58 brainstem nuclei spanning the midbrain, pons and medulla. We identify a compact set of integrative hubs in the brainstem with widespread connectivity with cerebral cortex. Patterns of connectivity between brainstem and cerebral cortex manifest as multiple emergent phenomena including neurophysiological oscillatory rhythms, patterns of cognitive functional specialization, and the unimodal-transmodal functional hierarchy. This persistent alignment between cortical functional topographies and brainstem nuclei is shaped by the spatial arrangement of multiple neurotransmitter receptors and transporters. We replicate all findings using 3 Tesla data from the same participants. Collectively, we find that multiple organizational features of cortical activity can be traced back to the brainstem.
PubMed: 38076888
DOI: 10.21203/rs.3.rs-3569352/v1 -
BioRxiv : the Preprint Server For... Oct 2023The brainstem is a fundamental component of the central nervous system yet it is typically excluded from human brain mapping efforts, precluding a complete...
The brainstem is a fundamental component of the central nervous system yet it is typically excluded from human brain mapping efforts, precluding a complete understanding of how the brainstem influences cortical function. Here we use high-resolution 7 Tesla fMRI to derive a functional connectome encompassing cortex as well as 58 brainstem nuclei spanning the midbrain, pons and medulla. We identify a compact set of integrative hubs in the brainstem with widespread connectivity with cerebral cortex. Patterns of connectivity between brainstem and cerebral cortex manifest as multiple emergent phenomena including neurophysiological oscillatory rhythms, patterns of cognitive functional specialization, and the unimodal-transmodal functional hierarchy. This persistent alignment between cortical functional topographies and brainstem nuclei is shaped by the spatial arrangement of multiple neurotransmitter receptors and transporters. We replicate all findings using 3 Tesla data from the same participants. Collectively, we find that multiple organizational features of cortical activity can be traced back to the brainstem.
PubMed: 37961347
DOI: 10.1101/2023.10.26.564245 -
Periodontology 2000 Feb 2024Peri-implantitis is a pathogenic inflammatory condition characterized by progressive bone loss and clinical inflammation that may compromise the stability of dental... (Review)
Review
Peri-implantitis is a pathogenic inflammatory condition characterized by progressive bone loss and clinical inflammation that may compromise the stability of dental implants. Therapeutic modalities have been advocated to arrest the disorder and to establish peri-implant health. Reconstructive therapy is indicated for bone defects exhibiting contained/angular components. This therapeutic modality is based upon the application of the biological and technical principles of periodontal regeneration. Nonetheless, the comparative efficacy of reconstructive therapy and nonreconstructive modalities remains unclear. Therefore, the aim of this narrative review is to address major clinical concerns regarding the efficacy, effectiveness, and feasibility of using biomaterials in peri-implantitis therapy. In particular, the use of bone grafting materials, barrier membranes, and biologics is comprehensively explored.
Topics: Humans; Peri-Implantitis; Biocompatible Materials; Bone Transplantation; Guided Tissue Regeneration, Periodontal; Bone Substitutes; Dental Implants; Bone Regeneration; Membranes, Artificial
PubMed: 37728141
DOI: 10.1111/prd.12523 -
European Radiology Jul 2023To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal...
OBJECTIVES
To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates.
METHODOLOGY
We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson's disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD).
RESULTS
MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons. CBD presented local atrophy in several small areas in the pons and midbrain compared to PD and CS. PSP presented local atrophy in small areas in the posterior and upper midbrain as well as the rostral pons compared to MSA. Our findings of planimetric MRI measurements and CSF NfL levels replicated those from previous literature. Brainstem shape atrophy correlated with worse motor state in all parkinsonisms and with higher NfL levels in MSA, PSP, and PD.
CONCLUSION
Atypical parkinsonisms present different brainstem shape patterns which correlate with clinical severity and neuronal degeneration. In MSA, shape analysis could be further explored as a potential diagnostic biomarker. By contrast, shape analysis appears to have a rather limited discriminant value in PSP.
KEY POINTS
• Atypical parkinsonisms present different brainstem shape patterns. • Shape patterns correlate with clinical severity and neuronal degeneration. • In MSA, shape analysis could be further explored as a potential diagnostic biomarker.
Topics: Humans; Pilot Projects; Retrospective Studies; Parkinsonian Disorders; Mesencephalon; Parkinson Disease; Pons; Magnetic Resonance Imaging; Multiple System Atrophy; Atrophy; Biomarkers; Diagnosis, Differential
PubMed: 36773046
DOI: 10.1007/s00330-023-09435-0