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1.
Nature ; 616(7955): 137-142, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36949192

RESUMO

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain1. For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved2. Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men1. Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium3-5. EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings3,6 but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation7,8. Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell-mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell-mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain.


Assuntos
Ansiedade , Células Enterocromafins , Dor Visceral , Feminino , Humanos , Masculino , Ansiedade/complicações , Ansiedade/fisiopatologia , Sistema Digestório/inervação , Sistema Digestório/fisiopatologia , Células Enterocromafins/metabolismo , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/psicologia , Caracteres Sexuais , Dor Visceral/complicações , Dor Visceral/fisiopatologia , Dor Visceral/psicologia , Inflamação/complicações , Inflamação/fisiopatologia , Serotonina/metabolismo , Reprodutibilidade dos Testes
2.
Nature ; 615(7951): 292-299, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36859543

RESUMO

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1-3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3-8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.


Assuntos
Comportamento Animal , Encéfalo , Emoções , Coração , Animais , Camundongos , Ansiedade/fisiopatologia , Encéfalo/fisiologia , Mapeamento Encefálico , Emoções/fisiologia , Coração/fisiologia , Comportamento Animal/fisiologia , Eletrofisiologia , Optogenética , Córtex Insular/fisiologia , Frequência Cardíaca , Channelrhodopsins , Taquicardia/fisiopatologia , Marca-Passo Artificial
3.
Behav Brain Res ; 432: 113983, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-35777551

RESUMO

Stroke continues to be a major cause of mortality globally. Post-stroke treatment is complicated by the heterogenous nature of pathology and the emergence of secondary psychological symptoms are an additional challenge to the recovery process. Poststroke depression (PSD) is a common co-morbidity and is a major impediment to recovery. While selective serotonin reuptake inhibitors (SSRIs) have proven to be clinically efficacious in treating PSD, the pathogenic processes that underlie the manifestation of depressive mood post-stroke remains unclear. Furthermore, the use of SSRIs is associated with risks of intracerebral haemorrhage, so alternative treatment options need to be continuously explored. Exercise has been demonstrated to be beneficial for improving mood in humans and preclinical models of neurological conditions. Little is known of the mood-related benefits of physical exercise post-stroke. Using the middle cerebral artery occlusion (MCAO) mouse model of cerebral ischaemia, we investigated whether behavioural deficits emerge post-MCAO and could be rescued by voluntary wheel-running. We report that MCAO induced hypo-locomotion and anhedonia-related behaviours, with some improvements conferred by wheel-running. Serotonin transporter gene expression was increased in the MCAO hippocampus and frontal cortex, but this increase remained despite wheel-running. Wheel-running associated up-regulation of BDNF gene expression was unaffected in MCAO mice, reflecting conservation of key neuroplasticity molecular pathways. Taken together, our results highlight the need for further research into serotonergic modulation of the affective symptoms of stroke.


Assuntos
Ansiedade , Depressão , Infarto da Artéria Cerebral Média , Condicionamento Físico Animal , Acidente Vascular Cerebral , Animais , Ansiedade/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Expressão Gênica , Infarto da Artéria Cerebral Média/complicações , Camundongos , Condicionamento Físico Animal/psicologia , Receptores de Serotonina , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico
4.
Science ; 377(6601): 27-28, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35771905

RESUMO

Social defeat activates midbrain cells, promoting sleep and reducing anxiety in mice.


Assuntos
Ansiedade , Mesencéfalo , Sono , Derrota Social , Estresse Psicológico , Animais , Ansiedade/fisiopatologia , Mesencéfalo/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Psicológico/fisiopatologia
5.
Sci Rep ; 12(1): 2434, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165331

RESUMO

Emerging evidence suggests that disruption of circadian rhythmicity contributes to development of comorbid depression, cardiovascular diseases (CVD), and type 2 diabetes mellitus (T2DM). Physical exercise synchronizes the circadian system and has ameliorating effects on the depression- and anxiety-like phenotype induced by circadian disruption in mice and sand rats. We explored the beneficial effects of voluntary wheel running on daily rhythms, and the development of depression, T2DM, and CVD in a diurnal animal model, the fat sand rat (Psammomys obesus). Voluntary exercise strengthened general activity rhythms, improved memory and lowered anxiety- and depressive-like behaviors, enhanced oral glucose tolerance, and decreased plasma insulin levels and liver weight. Animals with access to a running wheel had larger heart weight and heart/body weight ratio, and thicker left ventricular wall. Our results demonstrate that exercising ameliorates pathological-like daily rhythms in activity and blood glucose levels, glucose tolerance and depressive- and anxiety-like behaviors in the sand rat model, supporting the important role of physical activity in modulating the "circadian syndrome" and circadian rhythm-related diseases. We suggest that the utilization of a diurnal rodent animal model may offer an effective way to further explore metabolic, cardiovascular, and affective-like behavioral changes related to chronodisruption and their underlying mechanisms.


Assuntos
Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/terapia , Transtornos Cronobiológicos/complicações , Transtornos Cronobiológicos/terapia , Ritmo Circadiano , Depressão/complicações , Depressão/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício/métodos , Condicionamento Físico Animal/métodos , Animais , Ansiedade/complicações , Ansiedade/fisiopatologia , Ansiedade/terapia , Glicemia/análise , Doenças Cardiovasculares/fisiopatologia , Transtornos Cronobiológicos/fisiopatologia , Depressão/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Gerbillinae , Teste de Tolerância a Glucose , Insulina/sangue , Locomoção , Masculino , Ratos , Núcleo Supraquiasmático/fisiopatologia , Resultado do Tratamento
6.
Sci Rep ; 12(1): 1828, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115547

RESUMO

Maternal effects have been reported to alter offspring phenotype in laying hens. In this study, we investigated the effects of maternal environment and maternal age on egg traits and offspring development and behaviour. For this, we ran two experiments. First (E1), commercial hybrid hens were reared either in aviary or barren brooding cages, then housed in aviary, conventional cages or furnished (enriched) cages, thus forming different maternal housing treatments. Hens from each treatment were inseminated at three ages, and measures of egg composition, yolk testosterone concentration and offspring's development, anxiety and fearfulness were assessed. In experiment 2 (E2), maternal age effects on offspring's growth and behaviour were further investigated using fertile eggs from commercial breeder flocks at three different ages. Results from E1 showed that Old hens laid heavier eggs with less yolk testosterone and produced offspring with fewer indicators of anxiety and fearfulness. Maternal rearing and housing affected egg traits, offspring weight and behaviour, but not in a consistent way. Effects of maternal age were not replicated in E2, possibly due to differences in management or higher tolerance to maternal effects in commercial breeders. Overall, our research confirms that maternal age and maternal environment affects egg composition, with maternal age specifically affecting yolk testosterone concentration, which may mediate physical and behavioural effects in offspring.


Assuntos
Ansiedade/fisiopatologia , Galinhas/fisiologia , Testosterona/metabolismo , Zigoto/fisiologia , Fatores Etários , Animais , Ansiedade/metabolismo , Comportamento Animal/fisiologia , Peso Corporal , Gema de Ovo/química , Medo/fisiologia , Medo/psicologia , Feminino , Exposição Materna
7.
Nat Commun ; 13(1): 577, 2022 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-35102141

RESUMO

Emotional stress is considered a severe pathogenetic factor of psychiatric disorders. However, the circuit mechanisms remain largely unclear. Using a three-chamber vicarious social defeat stress (3C-VSDS) model in mice, we here show that chronic emotional stress (CES) induces anxiety-like behavior and transient social interaction changes. Dopaminergic neurons of ventral tegmental area (VTA) are required to control this behavioral deficit. VTA dopaminergic neuron hyperactivity induced by CES is involved in the anxiety-like behavior in the innate anxiogenic environment. Chemogenetic activation of VTA dopaminergic neurons directly triggers anxiety-like behavior, while chemogenetic inhibition of these neurons promotes resilience to the CES-induced anxiety-like behavior. Moreover, VTA dopaminergic neurons receiving nucleus accumbens (NAc) projections are activated in CES mice. Bidirectional modulation of the NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior. In conclusion, we propose that a NAc-VTA circuit critically establishes and regulates the CES-induced anxiety-like behavior. This study not only characterizes a preclinical model that is representative of the nuanced aspect of CES, but also provides insight to the circuit-level neuronal processes that underlie empathy-like behavior.


Assuntos
Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Vias Neurais/fisiopatologia , Núcleo Accumbens/fisiopatologia , Angústia Psicológica , Derrota Social , Área Tegmentar Ventral/fisiopatologia , Animais , Dependovirus/fisiologia , Depressão/fisiopatologia , Depressão/psicologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios GABAérgicos/metabolismo , Integrases/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Sinapses/metabolismo , Ácido gama-Aminobutírico/metabolismo
8.
J Integr Neurosci ; 21(1): 43, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35164479

RESUMO

Train and truck drivers experience a myriad of unique occupational factors, which have been postulated to contribute to a high incidence of health conditions such as depression anxiety and cardiovascular disease amongst this population. The present study aimed to identify associations between heart rate variability and negative mood states such as depression and anxiety in a cohort of Australian truck and train drivers. 120 professional drivers (60 truck drivers, 60 train drivers) were recruited from the local community. Participants complete a battery of psychometric questionnaires to assess levels of negative mood states such as depression and anxiety. Participants then completed a baseline (resting) and active (driving) task while concurrent electrocardiography data was collected to obtain heart rate variability parameters. Anxiety and depression were found to be associated with increases in low frequency heart rate variability and sympathovagal balance, and a reduction in total power. The present study identified associations between negative mood states and heart rate variability parameters that are unique to this cohort.


Assuntos
Ansiedade , Doenças Cardiovasculares , Depressão , Frequência Cardíaca/fisiologia , Doenças Profissionais , Adulto , Ansiedade/epidemiologia , Ansiedade/fisiopatologia , Austrália/epidemiologia , Condução de Veículo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Depressão/epidemiologia , Depressão/fisiopatologia , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Veículos Automotores , Doenças Profissionais/epidemiologia , Doenças Profissionais/fisiopatologia , Ferrovias , Adulto Jovem
9.
Molecules ; 27(4)2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35209199

RESUMO

Psoriasis is a common inflammatory skin disorder, which can be associated with psychological disorders, such as anxiety and depression. This study investigated the efficacy and the mechanism of action of a natural compound coptisine using imiquimod (IMQ)-induced psoriasis mice. Coptisine reduced the severity of psoriasis-like skin lesions, decreased epidermal hyperplasia and the levels of inflammatory cytokines TNF-α, IL-17, and IL-22. Furthermore, coptisine improved IMQ-induced anxiety in mice by increasing the number of entries and time in open arms in the elevated plus maze (EPM) test. Coptisine also lowered the levels of inflammatory cytokines TNF-α and IL-1ß in the prefrontal cortex of psoriasis mice. HaCaT keratinocytes and BV2 microglial cells were used to investigate the effects of coptisine in vitro. In M5-treated HaCaT cells, coptisine decreased the production of IL-6, MIP-3α/CCL20, IP-10/CXCL10, and ICAM-1 and suppressed the NF-κB signaling pathway. In LPS-stimulated BV2 cells, coptisine reduced the secretion of TNF-α and IL-1ß. These findings suggest that coptisine might be a potential candidate for psoriasis treatment by improving both disease severity and psychological comorbidities.


Assuntos
Ansiedade , Comportamento Animal/efeitos dos fármacos , Berberina/análogos & derivados , Imiquimode/efeitos adversos , Psoríase , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ansiedade/imunologia , Ansiedade/fisiopatologia , Berberina/farmacologia , Imiquimode/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/fisiopatologia
10.
Respir Physiol Neurobiol ; 298: 103847, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35066169

RESUMO

Allergic rhinitis (AR) is a chronic inflammatory disorder associated with a high prevalence of anxiety symptoms and respiratory disorders that adversely affect the quality of life. Studies have shown that allergen exposure induces anxiety-like behaviors. On the other hand, stress impairs the breathing pattern. However, the effect of stress on respiration and the relationship between anxiety-like behavior and stress-induced changes in breathing pattern has not been evaluated in AR. We assessed the impact of ovalbumin (OVA)-induced anxiety-like behaviors on stress-induced breathing pattern changes. Our findings showed that the allergic rhinitis induced by OVA challenge in sensitized rats induces anxiety-like behavior. Also, we found that stress decreases respiratory irregularity and increases respiratory variability, as well as the synchronization between IBI and RV time-series in AR animals. Moreover, in AR animals, we found a significant positive correlation between anxiety-like behavior and respiratory irregularity under non-stress conditions. Besides, a significant negative correlation was observed under stress conditions. The findings showed that anxiety-related behaviors may contribute to respiratory impairments under stress conditions in AR.


Assuntos
Ansiedade/fisiopatologia , Taxa Respiratória/fisiologia , Rinite Alérgica/fisiopatologia , Estresse Psicológico/fisiopatologia , Alérgenos/farmacologia , Animais , Ansiedade/induzido quimicamente , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Ovalbumina/farmacologia , Ratos
11.
Brain Res ; 1779: 147783, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35031297

RESUMO

Resilience refers to the ability to withstand or recover quickly from difficult conditions. Identification of the neurobiological mechanisms underlying resilience offers a novel way to the prevention and treatment of stress-induced psychiatric disorders such as depression. The septal nuclei have been described as an important node in emotional regulations. Metabotropic glutamate receptors (mGluRs) are abundantly expressed within the septum and play important regulatory roles in its neural activity. In this study, we assessed the functional roles of the mGlu2/3Rs and mGlu5Rs within different subregions of the septum in modulating stress resilience and vulnerability by using chronic social defeat stress (CSDS) paradigms in C57BL/6J male mice. Our results showed that approximately 47.9% of subjects exhibited anxiety- or depression-like behaviors after exposure to CSDS. The susceptible mice showed higher c-Fos expression in the lateral septal nucleus after confronted with an attacker. Compared with the resilient and control groups, the expression of mGlu2/3Rs was significantly down-regulated in the ventral part of lateral septal nucleus (LSv), but the expression of mGlu5Rs showed no significant difference among the three groups in the whole septum. Finally, we found the stress-induced social withdrawal symptoms could be rapidly relieved by intra-LSv injection of LY379268, an mGlu2/3Rs' agonist. Our findings point to an important role for mGlu2/3Rs in the LSv in promoting stress resilience and may provide potential new therapeutic targets for stress-induced psychiatric disorders, such as anxiety and depression.


Assuntos
Ansiedade , Depressão , Receptores de Glutamato Metabotrópico/metabolismo , Resiliência Psicológica/fisiologia , Núcleos Septais/metabolismo , Comportamento Social , Estresse Psicológico , Animais , Ansiedade/etiologia , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Depressão/etiologia , Depressão/metabolismo , Depressão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia
12.
J Clin Psychiatry ; 83(2)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35044728

RESUMO

Objective: In one of the largest and most comprehensive studies investigating the link between objective parameters of sleep and biological rhythms with peripartum mood and anxiety to date, we prospectively investigated the trajectory of subjective and objective sleep and biological rhythms, levels of melatonin, and light exposure from late pregnancy to postpartum and their relationship with depressive and anxiety symptoms across the peripartum period.Methods: One hundred women were assessed during the third trimester of pregnancy, of whom 73 returned for follow-ups at 1-3 weeks and 6-12 weeks postpartum. Participants were recruited from an outpatient clinic and from the community from November 2015 to May 2018. Subjective and objective measures of sleep and biological rhythms were obtained, including 2 weeks of actigraphy at each visit. Questionnaires validated in the peripartum period were used to assess mood and anxiety.Results: Discrete patterns of longitudinal changes in sleep and biological rhythm variables were observed, such as fewer awakenings (F = 23.46, P < .001) and increased mean nighttime activity (F = 55.41, P < .001) during postpartum compared to late pregnancy. Specific longitudinal changes in biological rhythm parameters, most notably circadian quotient, activity during rest at night, and probability of transitioning from rest to activity at night, were most strongly linked to higher depressive and anxiety symptoms across the peripartum period.Conclusions: Biological rhythm variables beyond sleep were most closely associated with severity of depressive and anxiety symptoms across the peripartum period. Findings from this study emphasize the importance of biological rhythms and activity beyond sleep to peripartum mood and anxiety.


Assuntos
Afeto , Ritmo Circadiano , Depressão Pós-Parto/fisiopatologia , Sono , Actigrafia , Adulto , Ansiedade/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Melatonina , Período Periparto/psicologia , Período Pós-Parto/psicologia , Gravidez , Terceiro Trimestre da Gravidez , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários
13.
Neuroimage ; 249: 118895, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35017125

RESUMO

Anxiety influences how the brain estimates and responds to uncertainty. The consequences of these processes on behaviour have been described in theoretical and empirical studies, yet the associated neural correlates remain unclear. Rhythm-based accounts of Bayesian predictive coding propose that predictions in generative models of perception are represented in alpha (8-12 Hz) and beta oscillations (13-30 Hz). Updates to predictions are driven by prediction errors weighted by precision (inverse variance) encoded in gamma oscillations (>30 Hz) and associated with the suppression of beta activity. We tested whether state anxiety alters the neural oscillatory activity associated with predictions and precision-weighted prediction errors (pwPE) during learning. Healthy human participants performed a probabilistic reward-based learning task in a volatile environment. In our previous work, we described learning behaviour in this task using a hierarchical Bayesian model, revealing more precise (biased) beliefs about the tendency of the reward contingency in state anxiety, consistent with reduced learning in this group. The model provided trajectories of predictions and pwPEs for the current study, allowing us to assess their parametric effects on the time-frequency representations of EEG data. Using convolution modelling for oscillatory responses, we found that, relative to a control group, state anxiety increased beta activity in frontal and sensorimotor regions during processing of pwPE, and in fronto-parietal regions during encoding of predictions. No effects of state anxiety on gamma modulation were found. Our findings expand prior evidence on the oscillatory representations of predictions and pwPEs into the reward-based learning domain. The results suggest that state anxiety modulates beta-band oscillatory correlates of pwPE and predictions in generative models, providing insights into the neural processes associated with biased belief updating and poorer learning.


Assuntos
Antecipação Psicológica/fisiologia , Ansiedade/fisiopatologia , Ondas Encefálicas/fisiologia , Córtex Cerebral/fisiopatologia , Eletroencefalografia , Aprendizagem por Probabilidade , Recompensa , Adulto , Feminino , Humanos , Masculino , Incerteza
14.
PLoS One ; 17(1): e0262916, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35089938

RESUMO

The current study aimed to further address important questions regarding the therapeutic efficacy of omega-3 fatty acids for various behavioral and neuroimmune aspects of the Fmr1 phenotype. To address these questions, our experimental design utilized two different omega-3 fatty acid administration timepoints, compared to both standard laboratory chow controls ("Standard") and a diet controlling for the increase in fat content ("Control Fat"). In the first paradigm, post-weaning supplementation (after postnatal day 21) with the omega-3 fatty acid diet ("Omega-3") reversed deficits in startle threshold, but not deficits in prepulse inhibition, and the effect on startle threshold was not specific to the Omega-3 diet. However, post-weaning supplementation with both experimental diets also impaired acquisition of a fear response, recall of the fear memory and contextual fear conditioning compared to the Standard diet. The post-weaning Omega-3 diet reduced hippocampal expression of IL-6 and this reduction of IL-6 was significantly associated with diminished performance in the fear conditioning task. In the perinatal experimental paradigm, the Omega-3 diet attenuated hyperactivity and acquisition of a fear response. Additionally, perinatal exposure to the Control Fat diet (similar to a "Western" diet) further diminished nonsocial anxiety in the Fmr1 knockout. This study provides significant evidence that dietary fatty acids throughout the lifespan can significantly impact the behavioral and neuroimmune phenotype of the Fmr1 knockout model.


Assuntos
Ansiedade , Comportamento Animal/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Proteína do X Frágil de Retardo Mental/genética , Hipocampo , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Ansiedade/dietoterapia , Ansiedade/genética , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Proteína do X Frágil de Retardo Mental/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Camundongos , Camundongos Knockout
15.
Neurosci Lett ; 771: 136390, 2022 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-34896437

RESUMO

Detrimental consequences following exposure to severe stress, either acute or chronic are well recognized. Chronic mild stress (CMS) is also a leading cause of emotional distress and neuropsychiatric conditions such as anxiety disorders. However, the neurobiological substrates of the latter, particularly at the ultrastructural levels have not been adequately investigated. In this study, adult male Wistar rats were subjected to 4 h daily mild restraint for 20 days and their behavior in open field and elevated plus maze (EPM) were evaluated 24 h after the last restraint. Anxiety-like behavior was evident in CMS exposed rats by increases in rearing and grooming in the open field and the avoidance of open arms in the EPM. Concomitant ultrastructural alterations such as chromatolysis, agglutination of synaptic vesicles or mitochondrial damage were also observed in the central nucleus of amygdala (CNA), an area intimately involved in emotional and fear response, in CMS exposed rats. These results while confirming detrimental consequences of CMS, also suggest that ultrastructural alterations in CNA may be a basis for CMS-induced anxiety.


Assuntos
Tonsila do Cerebelo/ultraestrutura , Ansiedade/patologia , Estresse Psicológico/patologia , Tonsila do Cerebelo/fisiopatologia , Animais , Ansiedade/etiologia , Ansiedade/fisiopatologia , Masculino , Aprendizagem em Labirinto , Mitocôndrias/ultraestrutura , Ratos , Ratos Wistar , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Vesículas Sinápticas/ultraestrutura
16.
Behav Brain Res ; 421: 113725, 2022 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-34929235

RESUMO

Stress, particularly during childhood, is a major risk factor for the development of depression. Depression is twice as prevalent in women compared to men, which suggests that biological sex also contributes to depression susceptibility. However, the neurobiology underpinning sex differences in the long-term consequences of childhood stress remains unknown. Thus, the aim of this study was to determine whether stress applied during the prepubertal juvenile period (postnatal day 27-29) in rats induces sex-specific changes in anxiety-like behaviour, anhedonia, and antidepressant-like behaviour in adulthood in males and females. The impact of juvenile stress on two systems in the brain associated with these behaviours and that develop during the juvenile period, the mesocorticolimbic dopaminergic system and hippocampal neurogenesis, were also investigated. Juvenile stress altered escape-oriented behaviours in the forced swim test in both sexes, decreased latency to drink a palatable substance in a novel environment in the novelty-induced hypophagia test in both sexes, and decreased open field supported rearing behavior in females. These behavioural changes were accompanied by stress-induced increases in tyrosine hydroxylase immunoreactivity in the prefrontal cortex of both sexes, but not other regions of the mesocorticolimbic dopaminergic system. Juvenile stress did not impact anhedonia in adulthood as measured by the saccharin preference test and had no effect hippocampal neurogenesis across the longitudinal axis of the hippocampus. These results suggest that juvenile stress has long-lasting impacts on antidepressant-like and reward-seeking behaviour in adulthood and these changes may be due to alterations to catecholaminergic innervation of the medial prefrontal cortex.


Assuntos
Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Depressão/fisiopatologia , Hipocampo/fisiologia , Neurogênese/fisiologia , Córtex Pré-Frontal/metabolismo , Recompensa , Estresse Psicológico/fisiopatologia , Fatores Etários , Anedonia/fisiologia , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Caracteres Sexuais
17.
Nephrology (Carlton) ; 27(2): 190-194, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34617354

RESUMO

The severe acute respiratory syndrome coronavirus (SARS-Cov-2) resulting in the coronavirus disease 2019 (COVID-19) is documented to have a negative psychosocial impact on patients. Home dialysis patients may be at risk of additional isolating factors affecting their mental health. The aim of this study is to describe levels of anxiety and quality of life during the COVID-19 pandemic among home dialysis patients. This is a single-centre survey of home dialysis patients in Toronto, Ontario. Surveys were sent to 98 home haemodialysis and 43 peritoneal dialysis patients. Validated instruments (Haemodialysis and Peritoneal Dialysis Treatment Satisfaction Questionnaire, Generalized Anxiety Disorder 7 Item [GAD7] Scale, Patient Health Questionnaire [PHQ-9], Illness Intrusiveness Ratings Scale, Family APGAR Questionnaire and The Self Perceived Burden Scale) assessing well-being were used. Forty of the 141 patients surveyed, participated in September 2020. The mean age was 53.1 ± 12.1 years, with 60% male, and 85% home haemodialysis, 80% of patients rated their satisfaction with dialysis at 8/10 or greater, 82% of respondents reported either "not at all" or "for several days" indicating frequency of anxiety and depressive symptoms, 79% said their illness minimally or moderately impacted their life, 76% of respondents were almost always satisfied with interactions with family members, 91% were never or sometimes worried about caregiver burden. Among our respondents, there was no indication of a negative psychosocial impact from the pandemic, despite the increased social isolation. Our data further supports the use of home dialysis as the optimal form of dialysis.


Assuntos
Ansiedade , COVID-19 , Hemodiálise no Domicílio , Falência Renal Crônica , Diálise Peritoneal , Ansiedade/diagnóstico , Ansiedade/fisiopatologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , Feminino , Hemodiálise no Domicílio/métodos , Hemodiálise no Domicílio/psicologia , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Saúde Mental , Pessoa de Meia-Idade , Ontário/epidemiologia , Diálise Peritoneal/métodos , Diálise Peritoneal/psicologia , Psicologia , Qualidade de Vida , SARS-CoV-2 , Isolamento Social , Inquéritos e Questionários
18.
Am J Med Genet A ; 188(1): 71-82, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536052

RESUMO

The coronavirus pandemic increased anxiety and stress and prevented access to health care worldwide; it is unclear how COVID-19 affected adults with a multisystem genetic disorder such as neurofibromatosis (NF). An anonymous online survey was distributed through an international registry and foundations to adults with NF (June-August 2020) to assess the impact of the pandemic on mental health and NF health care. Six hundred and thirteen adults (18-81 years; M = 45.7) with NF1 (77.8%), NF2 (14.2%), and schwannomatosis (7.8%) provided complete responses. Respondents rated moderate-to-high amounts of worry about the impact of COVID-19 on their emotional (46.3%) and physical health (46.7%), and 54.8% endorsed moderate-to-high pandemic-related stress. Adults with diagnosed/suspected mental health disorders or moderate-to-severe NF symptom impact as well as females endorsed higher COVID-19 stress (ps < 0.01). Less than half who missed a doctor's appointment for their NF care (43.4%) used telehealth. Of these, 33.3% and 46.2% reported that telehealth met their needs to a moderate or high degree, respectively. Results indicated that subgroups of adults with NF experience higher COVID-19-related worries and stress and may need additional support. Furthermore, telehealth is under-utilized and could help NF providers connect with patients, although improved delivery and patient training may facilitate expanded use of these services.


Assuntos
Ansiedade/psicologia , COVID-19/psicologia , Saúde Mental/estatística & dados numéricos , Neurofibromatoses/psicologia , Estresse Psicológico/fisiopatologia , Telemedicina/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/fisiopatologia , COVID-19/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibromatoses/fisiopatologia , SARS-CoV-2/patogenicidade , Inquéritos e Questionários , Estados Unidos/epidemiologia
19.
Behav Brain Res ; 419: 113681, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34838579

RESUMO

Serotonin transporter gene-linked polymorphic region polymorphisms are associated with anxiety, neuroticism, affective disorders and vulnerability to stressful life events; however, the relevant physiological mechanisms are not well understood. Serotonin transporter knockout mice have been widely used as a model of allelic variation of serotonin transporter function in humans; herein, wild-type mice and heterozygous and homozygous knockout mice models were established to explore the behavioural changes related to different genotypes and the possible physiological mechanisms. Behavioural changes were assessed using behavioural tests, namely, elevated plus maze, open field, Morris water maze and rotarod tests. Serum indicators were detected using the enzyme-linked immunosorbent assay. Compared with wild-type mice, homozygous mice showed significant anxiety-like behaviours in the plus maze and open field tests; conversely, anxiety-like behaviours in heterozygous mice were less pronounced. Homozygous mice also showed cognitive impairment and motor inhibition in the Morris water maze and rotarod tests. Serotonin levels decreased in both heterozygous and homozygous mice, and 5-hydroxytryptophan, protein kinase A, adenylyl cyclase, cyclic adenosine monophosphate response element-binding protein and brain-derived neurotrophic factor levels were lower in homozygous mice than in wild-type and heterozygous mice, whereas no statistical differences were found between wild-type and heterozygous mice. Additionally, there was a correlation between serological and behavioural indicators. This study provided experimental evidence that the cyclic adenosine monophosphate-protein kinase A-cyclic adenosine monophosphate response element-binding protein-brain-derived neurotrophic factor pathway may be involved in the regulation of polymorphism to stress and enriched the behavioural and physiological characteristics of serotonin transporter knockout mice.


Assuntos
Ansiedade , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Disfunção Cognitiva , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Atividade Motora , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Comportamento Animal/fisiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Knockout , Atividade Motora/fisiologia , Transdução de Sinais/fisiologia
20.
Behav Brain Res ; 419: 113679, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34826515

RESUMO

Alzheimer's disease (AD) affects several brain areas, including the prefrontal cortex (PFC) involved in execution, working memory, and fear extinction. Despite these critical roles, the PFC is understudied in AD pathology. People with post-traumatic stress disorder (PTSD) have twice the risk of developing AD, and the underlying mechanisms linking these two diseases are less understood. Here, we investigated the effect of footshock stress on behavioural vis-a-vis molecular changes in the PFC of an amyloid-beta (Aß)-42 lesion rat model of AD. Trauma-like conditions were induced by exposing the animals to several footshocks. AD-like condition was induced via intra-hippocampal injection of Aß-42 peptide. Following Aß-42 injections, animals were tested for behavioural changes using the Open Field Test (OFT) and Y-maze test. The PFC was later harvested for neurochemical analyses. Our results showed an interactive effect of footshocks and Aß-42 lesion on: reduced percentage alternation in the Y-maze test, suggesting memory impairment; reduced number of line crosses and time spent in the centre square of the OFT, indicating anxiogenic responses. Similarly, there was an interactive effect of footshocks and Aß-42 lesion on: increased FK506 binding protein 51 (FKBP5) expression, which can be associated with stress-induced anxiogenic behaviours; and increased neuronal apoptosis in the PFC of the animals. In addition, footshocks, as well as Aß-42 lesion, reduced superoxide dismutase levels and Bridging Integrator-1 (BIN1) expression in the PFC of the animals, which can be linked to the observed memory impairment. In conclusion, our findings indicate that footshocks exaggerate PFC-associated behavioural and molecular changes induced by an AD-like pathology.


Assuntos
Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/farmacologia , Ansiedade , Apoptose , Transtornos da Memória , Fragmentos de Peptídeos/farmacologia , Córtex Pré-Frontal , Transtornos de Estresse Pós-Traumáticos , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Animais , Ansiedade/induzido quimicamente , Ansiedade/etiologia , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Eletrochoque , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Transtornos de Estresse Pós-Traumáticos/induzido quimicamente , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Proteínas de Ligação a Tacrolimo/metabolismo
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