Chronic intermittent hypoxia elicits distinct transcriptomic responses among neurons and oligodendrocytes within the brainstem of mice. DOI
Hemalatha Bhagavan, Aguan Wei, Luíz M. Oliveira

и другие.

AJP Lung Cellular and Molecular Physiology, Год журнала: 2024, Номер 326(6), С. L698 - L712

Опубликована: Апрель 9, 2024

Chronic intermittent hypoxia (CIH) is a prevalent condition characterized by recurrent episodes of oxygen deprivation, linked to respiratory and neurological disorders. Prolonged CIH known have adverse effects, including endothelial dysfunction, chronic inflammation, oxidative stress, impaired neuronal function. These factors can contribute serious comorbidities, metabolic disorders cardiovascular diseases. To investigate the molecular impact CIH, we examined male C57BL/6J mice exposed for 21 days, comparing with normoxic controls. We used single-nucleus RNA sequencing comprehensively examine transcriptomic on key cell classes within brainstem, specifically excitatory neurons, inhibitory oligodendrocytes. regulate essential physiological functions, autonomic tone, control, respiration. Through analysis 10,995 nuclei isolated from pontine-medullary tissue, identified seven major classes, further subdivided into 24 clusters. Our findings among these revealed significant differential gene expression, underscoring their distinct responses CIH. Notably, neurons exhibited transcriptional dysregulation genes associated synaptic transmission, structural remodeling. In addition, found dysregulated encoding ion channels inflammatory response. Concurrently, oligodendrocytes phosphorylation stress. Utilizing CellChat network analysis, uncovered CIH-dependent altered patterns diffusible intercellular signaling. insights offer comprehensive cellular atlas pons-medulla provide fundamental resource adaptations triggered

Язык: Английский

The Retrotrapezoid Nucleus: Central Chemoreceptor and Regulator of Breathing Automaticity DOI
Patrice G. Guyenet, Ruth L. Stornetta, George M. P. R. Souza

и другие.

Trends in Neurosciences, Год журнала: 2019, Номер 42(11), С. 807 - 824

Опубликована: Окт. 18, 2019

Язык: Английский

Процитировано

162
The integrated brain network that controls respiration DOI Creative Commons
Friedrich Krohn, Manuele Novello, Ruben S. van der Giessen

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Март 8, 2023

Respiration is a brain function on which our lives essentially depend. Control of respiration ensures that the frequency and depth breathing adapt continuously to metabolic needs. In addition, respiratory control network has organize muscular synergies integrate ventilation with posture body movement. Finally, coupled cardiovascular emotion. Here, we argue can handle this all by integrating brainstem central pattern generator circuit in larger also comprises cerebellum. Although currently not generally recognized as center, cerebellum well known for its coordinating modulating role motor behavior, autonomic nervous system. review, discuss regions involved respiration, their anatomical functional interactions. We how sensory feedback result adaptation these mechanisms be compromised various neurological psychological disorders. demonstrate generators are part integrated regions.

Язык: Английский

Процитировано

85
Emergent Elements of Inspiratory Rhythmogenesis: Network Synchronization and Synchrony Propagation DOI Creative Commons
Sufyan Ashhad, Jack L. Feldman

Neuron, Год журнала: 2020, Номер 106(3), С. 482 - 497.e4

Опубликована: Март 3, 2020

Язык: Английский

Процитировано

86
Neuronal mechanisms underlying opioid-induced respiratory depression: our current understanding DOI
Jan‐Marino Ramirez, Nicholas Burgraff, Aguan Wei

и другие.

Journal of Neurophysiology, Год журнала: 2021, Номер 125(5), С. 1899 - 1919

Опубликована: Апрель 7, 2021

Opioid-induced respiratory depression (OIRD) represents the primary cause of death associated with therapeutic and recreational opioid use. Within United States, rate from abuse since early 1990s has grown disproportionally, prompting classification as a nationwide “epidemic.” Since this time, we have begun to unravel many fundamental cellular systems-level mechanisms opioid-related death. However, factors such individual vulnerability, neuromodulatory compensation, redundancy effects across central peripheral nervous systems created barrier concise, integrative view OIRD. review, bring together multiple perspectives in field OIRD create an overarching viewpoint what know, where essential topic research going forward into future.

Язык: Английский

Процитировано

76
PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate DOI Creative Commons
Clément Menuet, Angela A. Connelly, Jaspreet K. Bassi

и другие.

eLife, Год журнала: 2020, Номер 9

Опубликована: Июнь 15, 2020

Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, neurons entraining the activity pre-sympathetic parasympathetic cardiovascular neurons. Using a combination optogenetic inhibition excitation vivo situ rats, as well neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form kernel for inspiratory rhythm generation, directly modulate Specifically, inhibitory preBötC cardiac neuron whilst excitatory sympathetic vasomotor activity, generating heart respiration. Our data reveal yet more functions entrained to preBötC, role cardiorespiratory oscillations. The findings have implications pathologies, such hypertension failure, where entrainment diminished exaggerated.

Язык: Английский

Процитировано

72
Understanding and countering opioid‐induced respiratory depression DOI Open Access
Jordan T. Bateman, Sandy E. Saunders, Erica S. Levitt

и другие.

British Journal of Pharmacology, Год журнала: 2021, Номер 180(7), С. 813 - 828

Опубликована: Июнь 5, 2021

Respiratory depression is the proximal cause of death in opioid overdose, yet mechanisms underlying this potentially fatal outcome are not well understood. The goal review to provide a comprehensive understanding pharmacological opioid‐induced respiratory depression, which could lead improved therapeutic options counter as other detrimental effects opioids on breathing. development tolerance system also discussed, differences degree caused by various agonists. Finally, potential future agents aimed at reversing or avoiding through non‐opioid receptor targets and certain advantages over naloxone. By providing an overview network, will benefit research countering depression. LINKED ARTICLES This article part themed issue Advances Opioid Pharmacology Time Epidemic. To view articles section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc

Язык: Английский

Процитировано

69
Latent neural population dynamics underlying breathing, opioid-induced respiratory depression and gasping DOI Creative Commons
Nicholas E. Bush, Jan‐Marino Ramirez

Nature Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Янв. 5, 2024

Abstract Breathing is vital and must be concurrently robust flexible. This rhythmic behavior generated maintained within a rostrocaudally aligned set of medullary nuclei called the ventral respiratory column (VRC). The properties individual VRC are well known, yet technical challenges have limited interrogation entire population simultaneously. Here we characterize over 15,000 units using high-density electrophysiology, opto-tagging histological reconstruction. Population dynamics analysis reveals consistent rotational trajectories through low-dimensional neural manifold. These rotations even during opioid-induced depression. During severe hypoxia-induced gasping, reconfigure from to all-or-none, ballistic efforts. Thus, latent provide unifying lens onto activities large, heterogeneous populations neurons involved in simple, vital, breathing, describe how these respond variety perturbations.

Язык: Английский

Процитировано

11
Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network DOI Creative Commons
Nathan A. Baertsch, Nicholas E. Bush, Nicholas Burgraff

и другие.

eLife, Год журнала: 2021, Номер 10

Опубликована: Авг. 17, 2021

The analgesic utility of opioid-based drugs is limited by the life-threatening risk respiratory depression. Opioid-induced depression (OIRD), mediated μ-opioid receptor (MOR), characterized a pronounced decrease in frequency and regularity inspiratory rhythm, which originates from medullary preBötzinger Complex (preBötC). To unravel cellular- network-level consequences MOR activation preBötC, MOR-expressing neurons were optogenetically identified manipulated transgenic mice vitro vivo. Based on these results, model OIRD was developed silico. We conclude that hyperpolarization - expressing preBötC alone does not phenocopy OIRD. Instead, effects are twofold: (1) pre-inspiratory spiking reduced (2) excitatory synaptic transmission suppressed, thereby disrupting network-driven rhythmogenesis. These dual mechanisms opioid action act synergistically to make normally robust rhythm-generating network particularly prone collapse when challenged with exogenous opioids.

Язык: Английский

Процитировано

50
Multi-Level Regulation of Opioid-Induced Respiratory Depression DOI
Barbara Palković, Vitaliy Marchenko, Edward J. Zuperku

и другие.

Physiology, Год журнала: 2020, Номер 35(6), С. 391 - 404

Опубликована: Окт. 14, 2020

Opioids depress minute ventilation primarily by reducing respiratory rate. This results from direct effects on the preBötzinger Complex as well depression of Parabrachial/Kölliker-Fuse Complex, which provides excitatory drive to neurons mediating phase-switch. also awake forebrain and chemodrive.

Язык: Английский

Процитировано

45
Respiratory disorders of Parkinson’s disease DOI
Yasmin C. Aquino, Laís M. Cabral, Nicole C. Miranda

и другие.

Journal of Neurophysiology, Год журнала: 2021, Номер 127(1), С. 1 - 15

Опубликована: Ноя. 24, 2021

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in substantia nigra, mainly affecting people over 60 yr age. Patients develop both classic symptoms (tremors, muscle rigidity, bradykinesia, and postural instability) nonclassical (orthostatic hypotension, neuropsychiatric deficiency, sleep disturbances, respiratory disorders). Thus, patients with PD can have a significantly impaired quality life, especially when they do not multimodality therapeutic follow-up. The alterations associated this syndrome are main cause mortality PD. They be classified as peripheral caused disorders upper airways or muscles involved breathing central triggered functional deficits important located brainstem control. Currently, there little research describing these disorders, therefore, no well-established knowledge about subject, making treatment difficult. In review, history pathology data changes obtained thus far will addressed.

Язык: Английский

Процитировано

39