scholarly journals Sleep deprivation selectively down-regulates astrocytic 5-HT2B receptors and triggers depressive-like behaviors via stimulating P2X7 receptors

2019 ◽  
Author(s):  
Maosheng Xia ◽  
Shuai Li ◽  
Shanshan Liang ◽  
Xiaowei Li ◽  
Zexiong Li ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
P2x7 Receptors ◽  
Over Expression ◽  
Regulated Expression ◽  
Substantial Risk ◽  
Sleep Abnormalities ◽  
Underlying Mechanisms ◽  
Leucine Rich Repeat Protein

AbstractChronic loss of sleep damages health and disturbs quality of life. The long-lasting sleep deprivation (SD) as well as sleep abnormalities is a substantial risk factor for major depressive disorder (MDD), although the underlying mechanisms are not clear. In our previous studies, we report the activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome induced by long-term SD is P2X7 receptors (P2X7R) dependent, and antidepressant fluoxetine could alleviate this neuroinflammasome via 5-HT2B receptors (5-HT2BR) in astrocytes. Here, we discovered that the chronic SD activates astroglial P2X7 receptors, which in turn selectively down-regulated expression of 5-HT2BR in astrocytes. Stimulation of P2X7R induced by SD suppressed the phosphorylation of AKT and FoxO3a selectively in astrocytes, but not in neurones. The over-expression of FoxO3a in astrocytes inhibited expression of 5-HT2BR. Down-regulation of 5-HT2BR instigated by SD suppressed activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2 (cPLA2). This latter cascade promoted the release of arachidonic acid (AA) and prostaglandin E2 (PGE2). The depressive-like behaviours induced by SD were alleviated in P2X7R-KO mice. Our study reveals the mechanism underlying chronic SD-induced depressive-like behaviors and highlights that blocking P2X7 receptors or activating 5-HT2BR in astrocytes could play a key role for exploring the therapeutic strategies aimed at the depression evoked by sleep disorders.Main PointsChronic SD selectively down-regulates expression of 5-HT2BR through activation of P2X7R in astrocytes. SD promotes the release of AA and PGE2 via the decreased 5-HT2BR, these factors induce depressive-like behaviors.

scholarly journals SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

2021 ◽  
Vol 10 (15) ◽  
pp. 3441
Author(s):  
Hashir Ali Awan ◽  
Mufaddal Najmuddin Diwan ◽  
Alifiya Aamir ◽  
Muneeza Ali ◽  
Massimo Di Giannantonio ◽  
...  
Keyword(s):  
Olfactory Pathway ◽  
Cognitive Sequelae ◽  
Significant Burden ◽  
Inflammatory State ◽  
Underlying Mechanisms ◽  
Acute Changes ◽  
A Minor

The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual’s overall wellbeing, including adequate cognitive functioning. ‘Cognitive COVID’ is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of ‘Cognitive COVID’ as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of ‘Cognitive COVID.’ Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic’s unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.

scholarly journals The Role of Molecular Imaging as a Marker of Remyelination and Repair in Multiple Sclerosis

2021 ◽  
Vol 23 (1) ◽  
pp. 474
Author(s):  
Ido Ben-Shalom ◽  
Arnon Karni ◽  
Hadar Kolb
Keyword(s):  
Multiple Sclerosis ◽  
Molecular Imaging ◽  
Disease Progression ◽  
Acute Inflammation ◽  
Imaging Biomarkers ◽  
Underlying Mechanisms

The appearance of new disease-modifying therapies in multiple sclerosis (MS) has revolutionized our ability to fight inflammatory relapses and has immensely improved patients’ quality of life. Although remarkable, this achievement has not carried over into reducing long-term disability. In MS, clinical disability progression can continue relentlessly irrespective of acute inflammation. This “silent” disease progression is the main contributor to long-term clinical disability in MS and results from chronic inflammation, neurodegeneration, and repair failure. Investigating silent disease progression and its underlying mechanisms is a challenge. Standard MRI excels in depicting acute inflammation but lacks the pathophysiological lens required for a more targeted exploration of molecular-based processes. Novel modalities that utilize nuclear magnetic resonance’s ability to display in vivo information on imaging look to bridge this gap. Displaying the CNS through a molecular prism is becoming an undeniable reality. This review will focus on “molecular imaging biomarkers” of disease progression, modalities that can harmoniously depict anatomy and pathophysiology, making them attractive candidates to become the first valid biomarkers of neuroprotection and remyelination.

scholarly journals Fisetin Inhibits Osteoclast Differentiation via Downregulation of p38 and c-Fos-NFATc1 Signaling Pathways

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Sik-Won Choi ◽  
Young-Jin Son ◽  
Jung-Mi Yun ◽  
Seong Hwan Kim
Keyword(s):  
Biological Activities ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Inhibitory Effect ◽  
Over Expression ◽  
Expression Of Genes ◽  
Regulated Expression ◽  
Important Means ◽  
Bone Resorbing Activity

The prevention or therapeutic treatment of loss of bone mass is an important means of improving the quality of life for patients with disorders related to osteoclast-mediated bone loss. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Continus coggygria), exhibits various biological activities, but its effect on osteoclast differentiation is unknown. In this study, fisetin dose-dependently inhibited the RANKL-induced osteoclast differentiation with downregulation of the activity or expression of p38, c-Fos, and NFATc1 signaling molecules. The p38/c-Fos/NFATc1-regulated expression of genes required for cell fusion and bone resorption, such as DC-STAMP and cathepsin K, was also inhibited by fisetin. Considering the rescue of fisetin's inhibitory action by NFATc1 over-expression, the cascade of p38-c-Fos-NFATc1 could be strongly involved in the inhibitory effect of fisetin on osteoclast differentiation. Furthermore, fisetin inhibited the bone-resorbing activity of mature osteoclasts. In conclusion, fisetin may be of use in the treatment of osteoclast-related disorders, including osteoporosis.

scholarly journals Olfactory Disorders in Post-Acute COVID-19 Syndrome

Sinusitis ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 116-122
Author(s):  
Laura Araújo ◽  
Vanessa Arata ◽  
Ricardo G. Figueiredo
Keyword(s):  
Quality Of Life ◽  
Central Nervous System ◽  
Nervous System ◽  
Cellular Damage ◽  
The Central Nervous System ◽  
Olfactory Impairment ◽  
Underlying Mechanisms ◽  
Complex Scenario

Altered smell is one of the most prevalent symptoms in acute COVID-19 infection. Although most patients recover normal neurosensory function in a few weeks, approximately one-tenth of patients report long-term smell dysfunction, including anosmia, hyposmia, parosmia and phantosmia, with a particularly notable impact on quality of life. In this complex scenario, inflammation and cellular damage may play a key role in the pathogenesis of olfactory dysfunctions and may affect olfactory signaling from the peripheral to the central nervous system. Appropriate management of smell disturbances in COVID-19 patients must focus on the underlying mechanisms and the assessment of neurosensorial pathways. This article aims to review the aspects of olfactory impairment, including its pathophysiology, epidemiology, and clinical management in post-acute COVID-19 syndrome (PACS).

Thinking Beyond Language: Intervention for Severe Aphasia

2009 ◽  
Vol 19 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Nina Simmons-Mackie
Keyword(s):  
Quality Of Life ◽  
Communication Training ◽  
Language Intervention ◽  
Specific Training ◽  
Environmental Support ◽  
Total Communication ◽  
Communication Partners

Abstract Purpose: This article addresses several intervention approaches that aim to improve life for individuals with severe aphasia. Because severe aphasia significantly compromises language, often for the long term, recommended approaches focus on additional domains that affect quality of life. Treatments are discussed that involve increasing participation in personally relevant life situations, enhancing environmental support for communication and participation, and improving communicative confidence. Methods: Interventions that have been suggested in the aphasia literature as particularly appropriate for people with severe aphasia include training in total communication, training of communication partners, and activity specific training. Conclusion: Several intervention approaches can be implemented to enhance life with severe aphasia.

Communication Disordered: Program Implementation in Long-Term Care

2016 ◽  
Vol 1 (15) ◽  
pp. 64-67
Author(s):  
George Barnes ◽  
Joseph Salemi
Keyword(s):  
Program Implementation ◽  
Long Term Care ◽  
Family Satisfaction ◽  
Regulatory Compliance ◽  
Care Staff ◽  
Term Care ◽  
Staff Members ◽  
Change Policy

The organizational structure of long-term care (LTC) facilities often removes the rehab department from the interdisciplinary work culture, inhibiting the speech-language pathologist's (SLP's) communication with the facility administration and limiting the SLP's influence when implementing clinical programs. The SLP then is unable to change policy or monitor the actions of the care staff. When the SLP asks staff members to follow protocols not yet accepted by facility policy, staff may be unable to respond due to confusing or conflicting protocol. The SLP needs to involve members of the facility administration in the policy-making process in order to create successful clinical programs. The SLP must overcome communication barriers by understanding the needs of the administration to explain how staff compliance with clinical goals improves quality of care, regulatory compliance, and patient-family satisfaction, and has the potential to enhance revenue for the facility. By taking this approach, the SLP has a greater opportunity to increase safety, independence, and quality of life for patients who otherwise may not receive access to the appropriate services.

Long term follow-up in quality of life after mitral valve surgery

2012 ◽  
Vol 60 (S 01) ◽  
Author(s):  
I Kammerer ◽  
M Höhn ◽  
AH Kiessling ◽  
S Becker ◽  
FU Sack
Keyword(s):  
Quality Of Life ◽  
Mitral Valve ◽  
Mitral Valve Surgery ◽  
Valve Surgery ◽  
Long Term Follow Up

Long-term Outcome after Vegetative State due to Near-Drowning and Quality of Life of the Families

2012 ◽  
Vol 43 (02) ◽  
Author(s):  
G Kluger ◽  
A Kirsch ◽  
M Hessenauer ◽  
M Granel ◽  
A Müller ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Vegetative State ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Near Drowning
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