scholarly journals Hydroxychloroquine Increased Anxiety-Like Behaviors and Disrupted the Expression of Some Related Genes in the Mouse Brain

2021 ◽  
Vol 12 ◽  
Author(s):  
Hang Xu ◽  
Xiang Yang Zhang ◽  
Wei Wen Wang ◽  
Jiesi Wang
Keyword(s):  
Mental Health ◽  
Mrna Expression ◽  
Drug Administration ◽  
Psychiatric Symptoms ◽  
Clinical Investigation ◽  
Significant Risk ◽  
Prophylactic Drug ◽  
Dose Dependent ◽  
The Brain ◽  
Different Doses

Hydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for COVID-19, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta, corticotropin-releasing hormone (Crh), a serotonin transporter (Slc6a4), and a microglia maker (Aif1) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Lots of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders.

scholarly journals Hydroxychloroquine increased psychiatric-like behaviors and disrupted the expression of related genes in the mouse brain

2020 ◽  
Author(s):  
H Xu ◽  
XY Zhang ◽  
WW Wang ◽  
JS Wang
Keyword(s):  
Mental Health ◽  
Mrna Expression ◽  
Drug Administration ◽  
Psychiatric Symptoms ◽  
Clinical Investigation ◽  
Significant Risk ◽  
Prophylactic Drug ◽  
Dose Dependent ◽  
The Brain ◽  
Different Doses

AbstractHydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for SARS-COV-2, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days and enhanced depressive behavior at 24 h. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta and corticotropin-releasing hormone (Crh) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Most of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders.

scholarly journals Potential for imaging the high-affinity state of the 5-HT1B receptor: a comparison of three PET radioligands with differing intrinsic activity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anton Lindberg ◽  
Ryosuke Arakawa ◽  
Tsuyoshi Nogami ◽  
Sangram Nag ◽  
Magnus Schou ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Specific Binding ◽  
Occipital Cortex ◽  
Intrinsic Activity ◽  
High Affinity ◽  
G Protein Coupled ◽  
Dose Dependent ◽  
The Brain ◽  
Agonist Affinity States ◽  
Different Doses

Abstract Background Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT1B receptors. The 5-HT1B receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand. It is of interest to know whether the intrinsic activity of a PET radioligand for the 5-HT1B receptor impacts on its ability to detect changes in endogenous synaptic 5-HT density. Three high-affinity 11C-labeled 5-HT1B PET radioligands with differing intrinsic activity were applied to PET measurements in cynomolgus monkey to evaluate their sensitivity to be displaced within the brain by endogenous 5-HT. For these experiments, fenfluramine was pre-administered at two different doses (1.0 and 5.0 mg/kg, i.v.) to induce synaptic 5-HT release. Results A dose-dependent response to fenfluramine was detected for all three radioligands. At the highest dose of fenfluramine (5.0 mg/kg, i.v.), reductions in specific binding in the occipital cortex increased with radioligand agonist efficacy, reaching 61% for [11C]3. The most antagonistic radioligand showed the lowest reduction in specific binding. Conclusions Three 5-HT1B PET radioligands were identified with differing intrinsic activity that could be used in imaging high- and low-affinity states of 5-HT1B receptors using PET. From this limited study, radioligand sensitivity to endogenous 5-HT appears to depend on agonist efficacy. More extensive studies are required to substantiate this suggestion.

scholarly journals Role of Immunity in Pathogenesis of Psychosis

2021 ◽  
Author(s):  
Wafa Abdelghaffar ◽  
Oussama Sidhom ◽  
Lilia Laadhar ◽  
Rym Rafrafi
Keyword(s):  
Mental Health ◽  
Immune System ◽  
Psychiatric Symptoms ◽  
Scientific Evidence ◽  
Health Conditions ◽  
Future Research ◽  
Antineuronal Antibodies ◽  
System Components ◽  
The Brain

The involvement of immunity in the pathogenesis of schizophrenia and related psychoses was suspected a century ago but was shadowed by the dopaminergic hypothesis after the discovery of antipsychotics. We currently know that this latter theory has many limits and cannot account for the wide variety of psychotic conditions. The immune-inflammatory theory is now one of the most promising axes of research in terms of pathogenesis of several mental health conditions. Immunity and inflammation play a role at least in a subgroup of patients with psychosis. The immune system is complex with a variety of components and mediators that can all have effects on the brain and thus mediate psychiatric symptoms. In this chapter we will explore the scientific evidence of the role of immune system in pathophysiology of psychosis. The sections of this chapter will discuss the role of innate system components (cytokines, microglia, inflammation.), the role of adaptive system (lymphocytes and antibodies) with a section focusing on auto-immunity and particularly antineuronal antibodies. Finally we will discuss how this research can impact patients management and elaborate recommendations for future research.

scholarly journals Regular Moderate- to Vigorous-Intensity Physical Activity Rather Than Walking Is Associated with Enhanced Cognitive Functions and Mental Health in Young Adults

2020 ◽  
Vol 17 (2) ◽  
pp. 614 ◽  
Author(s):  
Takumi Nakagawa ◽  
Ibuki Koan ◽  
Chong Chen ◽  
Toshio Matsubara ◽  
Kosuke Hagiwara ◽  
...  
Keyword(s):  
Mental Health ◽  
Physical Activity ◽  
Young Adults ◽  
Cognitive Functions ◽  
Moderate Intensity ◽  
Health Measures ◽  
Intensity Physical Activity ◽  
Vigorous Intensity ◽  
Dose Dependent ◽  
The Brain

The beneficial effect of physical activity (PA) on the brain has been well established. Both acute and regular PA can boost a range of cognitive functions and enhance mood and mental health. Notably, the effect of acute PA on the brain and cognitive functions is generally found to be dose-dependent, in terms of both the amount and intensity of the exercise episode. In contrast, in the case of regular PA, the literature has primarily focused on the amount of exercise, and limited studies have assessed the influence of the exercise intensity. Since PA in higher intensity causes more extensive, more powerful, and longer-lasting neurobiological changes, it may prove more beneficial to cognitive functions and mental health. In the present study, we set out to test this hypothesis by employing a battery of questionnaires and laboratory tests with a sample of young adults. We found that more frequent vigorous- and moderate-intensity PA rather than walking (considered low to moderate intensity) was associated with better cognitive and mental health measures. Meanwhile, compared with no moderate- to vigorous-intensity physical activity (MVPA) at all, as few as 1~2 days per week (lasting at least 10 min each time) of MVPA was associated with a variety of benefits, particularly related to coping with challenging situations. In light of the neurobiological literature, the present study speaks to the value of moderate- to vigorous- rather than low-intensity PA in enhancing cognitive functions and mental health.

scholarly journals The effects of interleukin-10 and fibroblasts growth factor-2 in mice with toxic cuprizone model of demyelination

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
I. Labunets ◽  
A. Rodnichenko ◽  
N. Utko ◽  
T. Panteleimonova ◽  
Ya. Pokholenko ◽  
...  
Keyword(s):  
Nervous System ◽  
Growth Factor ◽  
Interleukin 10 ◽  
Antioxidant Defence ◽  
Positive Effects ◽  
Test Parameters ◽  
Human Proteins ◽  
Dose Dependent ◽  
The Brain ◽  
Different Doses

Cytokines and growth factors exhibit neurotropic, anti-inflammatory and immunomodulatory properties, and therefore can affect the functioning of the nervous system at demyelinating disorders.Purpose. To identify changes in T-lymphocytes, macrophages, oxidative stress and antioxidant defence factors, endocrine thymus function in the brain and behaviour of mice receiving neurotoxin cuprizone and recombinant human proteins: interleukin-10 (rhIL-10) and fibroblast growth factor (rhFGF-2).Materials and methods. 4-6-month-old 129/Sv mice received cuprizone with food every day for 3 weeks. From the 7th day of cuprizone diet, they received different doses of rhIL-10 and rhFGF-2. The content of СD3+ Т-cells, macrophages, malondialdehyde, activity of antioxidant enzymes in the brain and the level of thymulin in the blood were determined. Behavioural reactions were assessed in the “open field” test.Results. In the brain of mice receiving cuprizone and rhIL-10, there was a decrease in the number of СD3+ Т-cells and the activity of macrophages, which significantly increased under the influence of the toxin. After cytokine injection, the activity of superoxide dismutase, catalase and glutathione peroxidase increased significantly in the brain, as well as the level of thymulin in the blood. Motor, emotional and exploratory activity of mice, significantly suppressed by the cuprizone, was increased after the introduction of rhIL-10. The effect of rhIL-10 on the test parameters is more pronounced at a dose of 5 μg/kg than 50 μg/kg. After injection of rhFGF-2 in the mice with cuprizone diet, there is a decrease in the activity of brain macrophages and an increase of the level of thymulin in the blood depending on the dose of this factor; the motor activity of these animals increased regardless of the rhFGF-2 dose.Conclusion. The injections of rhIL-10 and rhFGF-2 provide dose-dependent positive effects on the pathogenetic factors of experimental demyelinating pathology, as well as the functional state of the nervous system. Whereas, the injections of rhIL-10 have more pronounced effects.

Localized vs. systemic inflammation in guinea pigs: a role for prostaglandins at distinct points of the fever induction pathways?

2005 ◽  
Vol 289 (2) ◽  
pp. R340-R347 ◽  
Author(s):  
Christoph Rummel ◽  
Stephan W. Barth ◽  
Thilo Voss ◽  
Stefan Korte ◽  
Rüdiger Gerstberger ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Prostaglandin E ◽  
Subcutaneous Injections ◽  
Local Site ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
Dose Dependent ◽  
The Brain ◽  
Different Doses

In guinea pigs, dose-dependent febrile responses were induced by injection of a high (100 μg/kg) or a low (10 μg/kg) dose of bacterial lipopolysaccharide (LPS) into artificial subcutaneously implanted Teflon chambers. Both LPS doses further induced a pronounced formation of prostaglandin E2 (PGE2) at the site of localized subcutaneous inflammation. Administration of diclofenac, a nonselective cyclooxygenase (COX) inhibitor, at different doses (5, 50, 500, or 5,000 μg/kg) attenuated or abrogated LPS-induced fever and inhibited LPS-induced local PGE2 formation (5 or 500 μg/kg diclofenac). Even the lowest dose of diclofenac (5 μg/kg) attenuated fever in response to 10 μg/kg LPS, but only when administered directly into the subcutaneous chamber, and not into the site contralateral to the chamber. This observation indicated that a localized formation of PGE2 at the site of inflammation mediated a portion of the febrile response, which was induced by injection of 10 μg/kg LPS into the subcutaneous chamber. Further support for this hypothesis derived from the observation that we failed to detect elevated amounts of COX-2 mRNA in the brain of guinea pigs injected subcutaneously with 10 μg/kg LPS, whereas subcutaneous injections of 100 μg/kg LPS, as well as systemic injections of LPS (intra-arterial or intraperitoneal routes), readily caused expression of the COX-2 gene in the guinea pig brain, as demonstrated by in situ hybridization. Therefore, fever in response to subcutaneous injection of 10 μg/kg LPS may, in part, have been evoked by a neural, rather than a humoral, pathway from the local site of inflammation to the brain.

scholarly journals Microglia Fighting for Neurological and Mental Health: On the Central Nervous System Frontline of COVID-19 Pandemic

2021 ◽  
Vol 15 ◽  
Author(s):  
Elisa Gonçalves de Andrade ◽  
Eva Šimončičová ◽  
Micaël Carrier ◽  
Haley A. Vecchiarelli ◽  
Marie-Ève Robert ◽  
...  
Keyword(s):  
Mental Health ◽  
Central Nervous System ◽  
Nervous System ◽  
Inflammatory Responses ◽  
Psychiatric Symptoms ◽  
Brain Parenchyma ◽  
Molecular Signature ◽  
The Central Nervous System ◽  
Psychiatric Manifestations ◽  
The Brain

Coronavirus disease 2019 (COVID-19) is marked by cardio-respiratory alterations, with increasing reports also indicating neurological and psychiatric symptoms in infected individuals. During COVID-19 pathology, the central nervous system (CNS) is possibly affected by direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion, exaggerated systemic inflammatory responses, or hypoxia. Psychosocial stress imposed by the pandemic further affects the CNS of COVID-19 patients, but also the non-infected population, potentially contributing to the emergence or exacerbation of various neurological or mental health disorders. Microglia are central players of the CNS homeostasis maintenance and inflammatory response that exert their crucial functions in coordination with other CNS cells. During homeostatic challenges to the brain parenchyma, microglia modify their density, morphology, and molecular signature, resulting in the adjustment of their functions. In this review, we discuss how microglia may be involved in the neuroprotective and neurotoxic responses against CNS insults deriving from COVID-19. We examine how these responses may explain, at least partially, the neurological and psychiatric manifestations reported in COVID-19 patients and the general population. Furthermore, we consider how microglia might contribute to increased CNS vulnerability in certain groups, such as aged individuals and people with pre-existing conditions.

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

Met and unmet needs among adults with mild to moderate intellectual disability with and without mental health problems

2020 ◽  
Author(s):  
Matthias Schützwohl
Keyword(s):  
Mental Health ◽  
Intellectual Disability ◽  
Unmet Needs ◽  
Mental Health Problems ◽  
Psychiatric Symptoms ◽  
Health Problems ◽  
Service Planning ◽  
Support Needs ◽  
Behaviour Problem ◽  
Prevalence Rates

Background: People with an intellectual disability (ID) show a great number and complex constellation of support needs. With respect to the planning of services, it is important to assess needs at the population level. ID services need to know to what extent support needs of clients with mental health problems differ from support needs of clients without any mental health problem.Aims: The aim of this study was to compare the prevalence rates of needs in relevant study groups. Methods: Data was generated from the MEMENTA-Study (“Mental health care for adults with intellectual disability and a mental disorder”). The Camberwell Assessment of Need for Adults with Intellectual Disabilities (CANDID) was used to assess met und unmet support needs. Data was available for n=248 adults with mild to moderate ID.Results: Mean total number of needs and unmet needs was associated with mental health status. However, in most particular areas under study, individuals without significant psychiatric symptoms or any behaviour problem needed as much as often help as individuals with such mental health problems. A higher rate of need for care among study participants with significant psychiatric symptoms or any behaviour problem was mainly found with regard to these specific areas (“minor mental health problems”, “major mental health problems”, “inappropriate behaviour”) or with regard to closely related areas (“safety of others”).Conclusions: Differences in prevalence rates mainly occurred in such areas of need that rather fall under the responsibility of mental health services than under the responsibility of ID services. This has implications for service planning.

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