COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

Cardiovascular Research, Journal Year: 2020, Volume and Issue: 116(10), P. 1666 - 1687

Published: April 14, 2020

Abstract The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of clinical course COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects lungs, causing interstitial pneumonitis severe acute respiratory distress syndrome (ARDS), it also multiple organs, particularly cardiovascular system. Risk infection mortality increase with advancing age male sex. Mortality is increased comorbidities: disease, hypertension, diabetes, chronic pulmonary cancer. most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) creatine kinase (CK) levels], fulminant myocarditis, heart failure, embolism, disseminated intravascular coagulation (DIC). Mechanistically, following proteolytic cleavage S protein serine protease, binds to transmembrane angiotensin-converting enzyme 2 (ACE2) —a homologue ACE—to enter type pneumocytes, macrophages, perivascular pericytes, cardiomyocytes. This may lead myocardial dysfunction damage, endothelial dysfunction, microvascular plaque instability, infarction (MI). ACE2 essential viral invasion, there no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) might be beneficial COVID-19. Initial immune inflammatory responses induce cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during rapid progression phase Early evaluation continued monitoring damage (cTnI NT-proBNP) (D-dimer) after hospitalization identify predict complications. Preventive measures (social distancing social isolation) risk. Cardiovascular therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, lopinavir/ritonavir, as well experimental therapies, such human recombinant (rhACE2), are discussed.

Language: Английский

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Neural mechanisms of social homeostasis

Annals of the New York Academy of Sciences, Journal Year: 2019, Volume and Issue: 1457(1), P. 5 - 25

Published: March 15, 2019

Social connections are vital to survival throughout the animal kingdom and dynamic across life span. There debilitating consequences of social isolation loneliness, support is increasingly a primary consideration in health care, disease prevention, recovery. Considering connection as an "innate need," it hypothesized that evolutionarily conserved neural systems underlie maintenance connections: alerting individual their absence coordinating effector mechanisms restore contact. This reminiscent homeostatic system designed maintain connection. Here, we explore identity regulating "social homeostasis." We review findings from rodent studies evaluating rapid response deficit (in form acute isolation) propose parallel, overlapping circuits engaged adapt vulnerabilities By considering other needs, such energy fluid balance, discuss potential attributes circuitry. reason uncovering these circuits/mechanisms will facilitate our understanding how loneliness perpetuates long-term states, which speculate may result sustained recruitment circuits.

Language: Английский

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Forgetting as a form of adaptive engram cell plasticity

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(3), P. 173 - 186

Published: Jan. 13, 2022

Language: Английский

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The neural circuitry of social homeostasis: Consequences of acute versus chronic social isolation

Cell, Journal Year: 2021, Volume and Issue: 184(6), P. 1500 - 1516

Published: March 1, 2021

Social homeostasis is the ability of individuals to detect quantity and quality social contact, compare it an established set-point in a command center, adjust effort expended seek optimal contact expressed via effector system. becomes positive or negative valence stimulus when deficient excess, respectively. Chronic deficits lead adaptations such that reintroduction previous optimum experienced as surplus. Here, we build upon models for include lasting changes environmental conditions, with chronic isolation.

Language: Английский

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The impact of loneliness and social isolation on the development of cognitive decline and Alzheimer’s Disease

Frontiers in Neuroendocrinology, Journal Year: 2023, Volume and Issue: 69, P. 101061 - 101061

Published: Feb. 8, 2023

Alzheimer's Disease (AD) is the leading cause of dementia, observed at a higher incidence in women compared with men. Treatments aimed improving pathology AD remain ineffective to stop disease progression. This makes detection early intervention strategies reduce future risk extremely important. Isolation and loneliness have been identified among major factors for AD. The increasing prevalence both emphasizes urgent need understand this association inform treatment. Here we present comprehensive review clinical preclinical studies that investigated social isolation as We discuss understanding mechanisms how exacerbates cognitive impairment focus on sex differences will shed light underlying regarding factor develop effective prevention or treatment strategies.

Language: Английский

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Engram neurons: Encoding, consolidation, retrieval, and forgetting of memory

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(8), P. 3207 - 3219

Published: June 27, 2023

Tremendous strides have been made in our understanding of the neurobiological substrates memory - so-called "engram". Here, we integrate recent progress engram field to illustrate how neurons transform across "lifespan" a from initial encoding, consolidation and retrieval, ultimately forgetting. To do so, first describe cell-intrinsic properties shape emergence at encoding. Second, highlight these encoding preferentially participate synaptic- systems-level memory. Third, changes during guide neural reactivation facilitate recall. Fourth, mechanisms forgetting, can counteract established consolidation, retrieval. Motivated by experimental results four sections, conclude proposing some conceptual extensions traditional view engram, including broadening cell-type participation within engrams stages. In collection, review synthesizes general principles stages, describes future avenues further understand dynamic engram.

Language: Английский

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Single housing‐induced effects on cognitive impairment and depression‐like behavior in male and female mice involve neuroplasticity‐related signaling

European Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 52(1), P. 2694 - 2704

Published: Aug. 31, 2019

Abstract Single‐housed stress elicits a range of social isolation‐related behavioral and neurobiological abnormalities. To investigate single housing‐induced changes sex differences on outcomes, we examined single‐housed stress‐induced learning memory impairment, depression‐like behaviors, neuroplasticity abnormalities underlying mechanism. The results showed that male female mice socially isolated for 8 weeks had significantly decreased acquisition, as demonstrated in the curve Morris water maze task. Memory consolidation retrieval were also both mice. These findings corroborated further by two classical animal models, Y‐maze novel object recognition tests, reduced spontaneous alternation index sexes Subsequent studies suggested exhibited increased immobility time forced swim tail suspension while only test. Moreover, apical basal branch points, dendritic length, spine density CA 1 hippocampal neurons effects consistent with neuroprotective‐related molecules such synaptophysin, PSD 95, PKA , pCREB BDNF expression. suggest loss neuronal remodeling neuroprotective mechanisms due to housing are involved provide evidence neuroplasticity‐related signaling plays crucial role isolation‐induced neuropsychiatric deficits sexes.

Language: Английский

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Social isolation alters behavior, the gut-immune-brain axis, and neurochemical circuits in male and female prairie voles

Neurobiology of Stress, Journal Year: 2020, Volume and Issue: 13, P. 100278 - 100278

Published: Nov. 1, 2020

The absence of social support, or isolation, can be stressful, leading to a suite physical and psychological health issues. Growing evidence suggests that disruption the gut-immune-brain axis plays crucial role in negative outcomes seen from isolation stress. However, mechanisms remain largely unknown. socially monogamous prairie vole (Microtus ochrogaster) has been validated as useful model for studying effects on brain behaviors, yet how gut microbiome central immune system are altered isolated voles still Here, we utilized this rodent examine stress alters relevant behaviors. Adult male female (n = 48 per sex) experienced were cohoused with same-sex cagemate (control) six weeks. Thereafter, their anxiety-like neuronal circuit activation, neurochemical expression, microgliosis key regions, well alterations treatment examined. Social increased behaviors impaired affiliation. Isolation also resulted sex- region-specific microgliosis. Further, correlated behavioral measures. Our data suggest sex-dependent manner microbes, glial cells, systems may play critical, integrative mediating isolation.

Language: Английский

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Inhibition of Rac1-dependent forgetting alleviates memory deficits in animal models of Alzheimer’s disease

Protein & Cell, Journal Year: 2019, Volume and Issue: 10(10), P. 745 - 759

Published: July 18, 2019

Accelerated forgetting has been identified as a feature of Alzheimer’s disease (AD), but the therapeutic efficacy manipulation biological mechanisms not assessed in AD animal models. Ras-related C3 botulinum toxin substrate 1 (Rac1), small GTPase, shown to regulate active Drosophila and mice. Here, we showed that Rac1 activity is aberrantly elevated hippocampal tissues patients Moreover, amyloid-beta 42 could induce activation cultured cells. The elevation only accelerated 6-hour spatial memory decay 3-month-old APP/PS1 mice, also significantly contributed severe loss aged A similar age-dependent activity-based was observed an fly model. inhibition ameliorate cognitive defects synaptic plasticity Finally, two novel compounds, through behavioral screening randomly selected pool brain permeable molecules for their positive effect rescuing both mouse models, were found be capable inhibiting activity. Thus, multiple lines evidence corroborate supporting idea effective treating AD-related loss.

Language: Английский

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The Role of Rac GTPase in Dendritic Spine Morphogenesis and Memory

Frontiers in Synaptic Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: April 17, 2020

The ability to form memories in the brain is an important process needed for daily functions and its impairment associated with human mental disorders. Evidence indicates that long-term memory (LTM) related processes such as consolidation, extinction forgetting involve changes of synaptic efficacy produced by alterations neural transmission morphology. Modulation number dendritic spines their morphology has been proposed contribute neuronal mediating LTM processes. Rac GTPase activity regulated activation it can affect spine controlling actin-regulatory proteins. Recent evidence shows extinction, erasure areas mediate these behaviors. Altered abnormal By affecting we further understand roles morphogenesis memory. Moreover, manipulation may serve a therapeutic tool treatment memory-related diseases.

Language: Английский

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