RESUMO
Group work is essential in professional settings to encourage effective communication and optimize outcomes. Stress can reduce teamwork effectiveness and aromatherapy might be able to reduce feelings of stress/anxiety in individuals. However, it is unclear if aromatherapy impacts stress levels or performance during group activities. Therefore, we examined if essential oil exposure impacted stress responses and performance of individuals and groups during a team-based task involving a challenging medical decision. Subjects (n = 36) were part of a 3-person group (12 groups total) that completed a timed moral reasoning dilemma wearing a mask that contained a purported stimulatory essential oil (peppermint), a purported relaxing essential oil (lavender) or masks that contained neither odor (3 groups/mask type). Heart rate (HR) responses were recorded continuously before, during and after the task. The time to complete the task, decision making during the task, and subject's perceptions of the task were also recorded. Control subjects and subjects exposed to peppermint demonstrated a significant stress-induced increase in HR during the group task. However, subjects exposed to lavender demonstrated a significantly attenuated HR. Subjects in the control group who perceived high stress levels during the task demonstrated further elevations in HR than those not reporting stress, however, this pattern was not observed in subjects exposed to either essential oil. Groups did not differ in the time required to complete the task although only the groups exposed to lavender used decision making consistent with medical practice. Therefore, exposure to lavender was associated with differential physiological responses during a stressful group task, potentially due to olfactory system stimulation of anxiolytic and/or trust promoting central nervous system pathways. Aromatherapy might be a useful tool in group settings to mitigate the impact of stress and improve group performance.
Assuntos
Lavandula , Óleos Voláteis , Processos Grupais , Humanos , Óleos Voláteis/farmacologia , Óleos de Plantas , Estudantes , UniversidadesRESUMO
The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment than traditional treatment methods. Although the combination of target therapy with nanotechnology created new hope for cancer treatment, methodological issues during in vitro validation of nanovehicles slowed their application. In the current work, the effect of methotrexate (MTX) encapsulated in different matrices was evaluated in a dynamic microfluidic platform. Effects on the viability of osteosarcoma cells in the presence of recirculation of cell media, free MTX and two types of blank and drug-containing nanoparticles were successfully assessed in different tumor-mimicking microenvironments. Encapsulated MTX was more effective than the equal dose free drug treatment, as cell death significantly increased under the recirculation of both types of drug-loaded nanoparticles in all concentrations. In fact, MTX-nanoparticles reduced cell population 50 times more than the free drug when 150-µM drug dose was recirculated. Moreover, when compared to the equivalent free drug dose recirculation, cell number was reduced 60 and 100 points more under recirculation of each nanoparticle with a 15-µM drug concentration. Thus, the results obtained with the microfluidic model present MTX-lipid nanoparticles as a promising and more effective therapy for pediatric osteosarcoma treatment than current treatment options.
RESUMO
Increased access to electronic devices and the ubiquity of social media has resulted in a rapid rise in the prevalence of students "multitasking" while in a classroom setting. While some data indicate the use of electronic devices in class can improve the classroom environment, other studies demonstrate the opposite finding. Moreover, it remains unclear if using social networking sites such as Instagram impacts performance on cognitive tasks when students are presented new material and, if so, what features of Instagram modulate this response. Therefore, in the current study we examined if social media use during or after being presented new information affected short-term memory in college students. Additionally, we assessed if the type or quantity of topics displayed had a modulatory impact on memory. Forty-five college-aged (18-24 years of age) students completed the Logical Memory Immediate Recall (LM I) component of the Wechsler Memory Scale IV, a measure of auditory recognition memory. Subjects were randomly divided into a group that completed the LM I without distraction (controls), a group that completed the LM I while scrolling through their Instagram feed, or a group that completed the LM I after scrolling through their Instagram feed. Subjects that used Instagram while being presented new information demonstrated worse short-term memory recall ability compared to subjects that did not use Instagram during the presentation (71.56% correct answers vs. 80.89%; p = 0.01). Recall ability in the group that used Instagram after hearing the story was not statistically different from the controls. Differences were not observed in the number of topics appearing in subjects' Instagram feeds and no correlation was found between the number of topics on a subject's Instagram feed and memory recall ability. Collectively, these results suggest that individuals who use their phones to browse Instagram during class or in social settings might have a reduced ability to retain the information given to them when compared to those that are not using their phones scrolling on social media.
Assuntos
Memória de Curto Prazo , Mídias Sociais , Humanos , Rede Social , Estudantes , Universidades , Adulto JovemRESUMO
Recent evidence indicates that social network use (e.g., Facebook) prior to exposure to an acute stressor can buffer the physiological response to that stressor. However, it is unclear if using social media after exposure to an acute stressor can modulate recovery following the stressor. In the current study, therefore, we examined if social media use might serve as an effective coping mechanism to help deal with exposure to a stressor. Heart rate, blood pressure, and salivary cortisol were compared in healthy college undergraduates (n = 23) before and after completion of the Trier Social Stress Test (TSST). Following exposure to the TSST, subjects were selected to use social media, read quietly or given the choice to use social media or read quietly during a 15- minute recovery period. The TSST induced significant increases in heart rate, systolic blood pressure, and salivary cortisol. Additional analyses revealed that subjects that used social media after termination of the acute stressor demonstrated a significantly facilitated hemodynamic and a trend for a more rapid endocrine recovery compared with subjects that read quietly during the recovery period. Although the majority (71%) of subjects given the choice of recovery modality chose to use social media, differences were not observed between groups selected to use social media and those given the choice to do so during the recovery period. These results suggest that sympathetic nervous system and hypothalamic-pituitary-adrenal axis recovery following stimulation by an acute stressor might be modulated by social media use in undergraduates. Collectively, these data provide further insight into the interaction between psychosocial stress, social media use and health.
Assuntos
Mídias Sociais , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Saliva , Estresse PsicológicoRESUMO
Cardiovascular disease (CVD) remains the leading cause of disease burden globally and chronic stress is associated with increased risk of CVD. Recognition of chronic occupational stressors as a potential contributor to CVD highlights the need to recognize and prevent stress during work. The ubiquity of wearable technology devices to monitor health provides a new opportunity to noninvasively examine the cardiovascular system throughout a work shift. In the current study, we examined changes in heart rate (HR) during a work shift in a retail store setting using 23 healthy female and male subjects that differed in their physical fitness status. Subjects had their HR tracked via an Apple Watch during three typical work shifts. The results demonstrated an increase in HR during a work shift to a level observed during a moderate stressor (resting HR = 83.2 BPM ± 7.8; highest HR mean = 109.1 BPM ± 11.7; p < .0001). Female subjects demonstrated a significantly elevated maximum HR, a larger change in HR, and a larger percent change in HR compared with males (all p < .05). Physical activity status did not influence the observed changes in HR for females or males. Neither the time of day the work shift occurred nor the length of the shift modulated the observed pattern of HR changes. Collectively, our findings demonstrate the potential for wearables in biomedical research and personalized health.
Assuntos
Frequência Cardíaca/fisiologia , Estresse Ocupacional/fisiopatologia , Adulto , Doenças Cardiovasculares , Exercício Físico , Feminino , Humanos , Masculino , Monitorização Fisiológica , Fatores Sexuais , Dispositivos Eletrônicos VestíveisRESUMO
While the number of individuals participating in internet-based social networks has continued to rise, it is unclear how participating in social networks might influence quality of life (QOL). Individuals differ in their experiences, motivations for, and amount of time using internet-based social networks, therefore, we examined if individuals differing in social network user experiences, motivations and frequency of social network also differed in self-reported QOL. Two-hundred and thirty-seven individuals (aged 18-65) were recruited online using the online platform Mechanical Turk (MTurk). All participants completed a web-based survey examining social network use and the World Health Organization Quality of Life Scale Abbreviated Version (WHOQOL-Bref) to assess QOL. Individuals who reported positive associations with the use of social networks demonstrated higher QOL while those reporting negative associates demonstrated lower QOL. Moreover, individuals using social networks to stay connected to friends demonstrated higher QOL while those using social networking for dating purposes reported lower QOL. Frequency of social network use did not relate to QOL. These results suggest that QOL differs among social network users. Thus, participating in social networking may be a way to either promote or detract from QOL.
Assuntos
Internet/tendências , Motivação , Qualidade de Vida/psicologia , Mídias Sociais/tendências , Rede Social , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação/fisiologia , Inquéritos e Questionários , Adulto JovemRESUMO
Having a large social network is generally beneficial to health. However, it is unclear how Internet-based social networks might influence health. Chronic stress can have negative health consequences, and some data suggest that Facebook could be a new source of psychological stress. Thus, we examined undergraduate college student perceptions of Facebook use and incidence of upper respiratory infections (URIs). We hypothesized that subjects with more diverse networks (i.e., more friends on Facebook) would have fewer URIs than their less diverse counterparts; that subjects reporting Facebook-induced stress would be more susceptible to URIs; and that subjects with more diverse networks who report Facebook-induced stress would be less susceptible to URIs than subjects with less diverse social networks who reported Facebook-induced stress. In this prospective study, healthy college students completed online questionnaires that assessed use and perceptions of Facebook and technology, and then were interviewed weekly for 10 weeks to track incidence of URI. URI episodes were defined by a symptom-based criterion. The social network size was significantly related to the rate of URI, such that, the larger the social network, the greater the incidence rate of URI. Most (85.7 percent) respondents experienced some degree of Facebook-induced stress. The effects of Facebook-induced stress on incidence of URI varied across the social network size, such that, the impact of stress on the URI incidence rate increased with the size of the social network. These results are largely in contrast to our hypotheses, but clearly suggest an association between Facebook use, psychological stress, and health.
Assuntos
Infecções Respiratórias/complicações , Comportamento Social , Rede Social , Apoio Social , Estresse Psicológico/complicações , Adolescente , Atitude Frente aos Computadores , Resistência à Doença , Feminino , Humanos , Relações Interpessoais , Masculino , Estudos Prospectivos , Infecções Respiratórias/psicologia , Estudantes , Universidades , Adulto JovemRESUMO
Undergraduate students routinely experience acute psychosocial stress when interviewing for post-collegiate employment. While numerous studies have demonstrated that acute stress can increase release of immune-relevant molecules in blood, fewer studies have examined if acute stress also increases immune-relevant molecules into saliva. Saliva, and the biomolecules found in saliva often serve important immune defense roles and can be used to non-invasively screen for many systemic diseases. Therefore, the current study examined saliva concentrations of endocrine and immune molecules following exposure to an acute psychosocial stressor (mock job interview) in undergraduates. Heart rate, blood pressure, salivary cortisol, salivary immunoglobulin-A (S-IgA), and salivary C-reactive protein (S-CRP) were compared in healthy college undergraduates (n=15) before and after completion of the Trier Social Stress Test (TSST). The TSST induced significant increases in heart rate, systolic blood pressure, and salivary cortisol. Additional analyses revealed a non-significant (p=0.1) increase in the level of S-IgA following the TSST. A significant decrease in S-IgA was observed during the recovery period. No change in S-CRP was observed following the TSST. These results suggest that acute stress experienced by undergraduates when interviewing for a job activates the sympathetic nervous system and hypothalamic-pituitary-adrenal axis and that cortisol levels increase in saliva. Stress-induced elevations in cortisol might be responsible for the decreased S-IgA observed following the recovery period. Collectively, these data provide further insight into the interaction between psychosocial stress, endocrine, and immune functioning.
Assuntos
Hidrocortisona/metabolismo , Imunoglobulina A/metabolismo , Saliva/metabolismo , Estresse Psicológico/imunologia , Estresse Psicológico/metabolismo , Adolescente , Análise de Variância , Pressão Sanguínea/fisiologia , Proteína C-Reativa/metabolismo , Feminino , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Humanos , Masculino , Estresse Psicológico/fisiopatologia , Estudantes , Universidades , Adulto JovemRESUMO
Activation of the in vivo stress response can facilitate antibacterial host defenses. One possible mechanism for this effect is stress-induced release of heat shock protein 72 (Hsp72) into the extracellular environment. Hsp72 is a ubiquitous cellular protein that is up-regulated in response to cellular stress, and modulates various aspects of immune function including macrophage inflammatory/bactericidal responses and T-cell function when found in the extracellular environment. The current study tested the hypothesis that in vivo extracellular Hsp72 (eHsp72) at the site of inflammation contributes to stress-induced restricted development of bacteria, and facilitated recovery from bacteria-induced inflammation, and that this effect is independent of alpha beta (αß) T cells. Male F344 rats were exposed to either inescapable electrical tail-shocks or no stress, and subcutaneously injected with Escherichia coli (ATCC 15746). The role of eHsp72 was investigated by Hsp72-immunoneutralization at the inflammatory site. The potential contribution of T cells was examined by testing male athymic (rnu/rnu) nude rats lacking mature αß T cells and heterozygous thymic intact control (rnu/+) rats. The results were that stressor exposure increased plasma concentrations of eHsp72 and facilitated recovery from bacterial inflammation. Immunoneutralization of eHsp72 at the inflammatory site attenuated this effect. Stressor exposure impacted bacterial inflammation and eHsp72 equally in both athymic and intact control rats. These results support the hypothesis that eHsp72 at the site of inflammation, and not αß T cells, contributes to the effect of stressor exposure on subcutaneous bacterial inflammation.
Assuntos
Infecções por Escherichia coli/fisiopatologia , Proteínas de Choque Térmico HSP72/metabolismo , Inflamação/microbiologia , Estresse Psicológico/fisiopatologia , Linfócitos T/fisiologia , Animais , Eletrochoque , Proteínas de Choque Térmico HSP72/sangue , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos NusRESUMO
To increase student engagement, active participation, and performance, personal response systems (clickers) were incorporated into six lecture-based sections of four required courses within the Health Sciences Department major curriculum: freshman-level Anatomy and Physiology I and II, junior-level Exercise Physiology, and senior-level Human Pathophysiology. Clickers were used to gather anonymous student responses to questions posed within the class period after individual thought and peer discussion. Students (n = 293, 88% of students completing the courses) completed a perceptual survey on clicker effectiveness inserted into the Student Assessment of Learning Gains online instrument. Across courses and years, students uniformly rated several dimensions of clicker use as providing good to great gain in engaging them in active learning, increasing participation and involvement during class, maintaining attention, applying material immediately, providing feedback concerning their understanding, and offering an anonymous format for participation. Within these four sections, quiz grades were compared between clicker and nonclicker years. Significant increases in pre- and posttest scores were seen in Exercise Physiology in clicker years and on some, but not all material, in Anatomy and Physiology I and II based on content quizzes. Human Pathophysiology results were unexpected, with higher quiz scores in the nonclicker year. The results support the hypothesis of increased engagement with clicker use. The hypothesis of increased student performance was not consistently supported. Increased performance was seen in Exercise Physiology. In Anatomy and Physiology I and II, performance improved on some content quizzes. In Human Pathophysiology, performance did not improve with clickers.
Assuntos
Currículo , Fisiologia/educação , Estudantes/psicologia , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: The role of histocompatibility and immune recognition in stem cell transplant therapy has been controversial, with many reports arguing that undifferentiated stem cells are protected from immune recognition due to the absence of major histocompatibility complex (MHC) markers. This argument is even more persuasive in transplantation into the central nervous system (CNS) where the graft rejection response is minimal. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we evaluate graft survival and neuron production in perfectly matched vs. strongly mismatched neural stem cells transplanted into the hippocampus in mice. Although allogeneic cells survive, we observe that MHC-mismatch decreases surviving cell numbers and strongly inhibits the differentiation and retention of graft-derived as well as endogenously produced new neurons. Immune suppression with cyclosporine-A did not improve outcome but non-steroidal anti-inflammatory drugs, indomethacin or rosiglitazone, were able to restore allogeneic neuron production, integration and retention to the level of syngeneic grafts. CONCLUSIONS/SIGNIFICANCE: These results suggest an important but unsuspected role for innate, rather than adaptive, immunity in the survival and function of MHC-mismatched cellular grafts in the CNS.
Assuntos
Diferenciação Celular , Teste de Histocompatibilidade , Complexo Principal de Histocompatibilidade/imunologia , Células-Tronco Neurais/transplante , Neurogênese , Neurônios/citologia , Transplante de Células-Tronco , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Diferenciação Celular/efeitos dos fármacos , Apresentação Cruzada/efeitos dos fármacos , Ciclosporina/farmacologia , Citocinas/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Hipocampo/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transplante HomólogoRESUMO
Many undergraduate institutions offer individual research opportunities for upper-level students in independent study courses and summer undergraduate research programs. These are necessarily limited to a small number of students. Greater numbers of students can benefit from incorporating student-directed investigative experiences into laboratories in standard courses. In human performance investigations, any single course may not offer sufficient numbers of subjects to adequately test hypotheses comparing population groups or to examine longitudinal trends. In this exercise physiology course, exercise testing was conducted in three areas: 1) techniques of body composition analysis, 2) field tests for the estimation of maximal oxygen consumption, and 3) maximal anaerobic and aerobic power. All students enrolled over a 10-yr period participated as subjects and as testers. Working in small research groups, students added their results to those from previous years, generated a variety of hypotheses (correlations between tests, subgroup differences, etc.), and tested them statistically using the complete data set of 217 subjects. They then engaged in collaborative writing and peer review to prepare formal papers on their results. The multiyear approach allowed students to situate their work within and contribute to the accumulation of a large database and to practice essential scientific skills of hypothesis formation, data collection and analysis, collaborative work, and scientific communication. In addition, due to the larger number of subjects available to analyze, students observed statistically significant differences between test groups in the multiyear database that they were unable to demonstrate when conducting analysis on a single course. Finally, the large number of subjects and statistical power offered by the use of the database provides distinct pedagogical advantages.
Assuntos
Exercício Físico/fisiologia , Fisiologia/educação , Fisiologia/tendências , Estudantes de Ciências da Saúde , Universidades/tendências , Feminino , Humanos , Masculino , Fatores de TempoRESUMO
Heat-shock protein concentrations in the blood increase after exposure to a variety of stressors, including trauma and psychological stress. Although the physiological function of extracellular heat shock protein remains controversial, there is evidence that extracellular heat shock protein 72 (Hsp72) can facilitate immunologic responses. The signal(s) that mediate(s) the in vivo elevation of extracellular Hsp72 in the blood after stressor exposure remain(s) unknown. Here we report that Hsp72 increases in the circulation via an alpha1-adrenergic receptor-mediated signaling pathway. Activation of alpha1-adrenoceptors results in a rapid increase in circulating Hsp72, and blockade of alpha1-adrenoceptors prevents the stress-induced rise in circulating Hsp72. Furthermore, our studies exclude a role for beta-adrenoceptors, glucocorticoids, and ACTH in mediating stress-induced elevations in circulating extracellular Hsp72. Understanding the signals involved in elevating extracellular Hsp72 could facilitate the use of extracellular Hsp72 to bolster immunity and perhaps prevent exacerbation of inflammatory diseases during stress.
Assuntos
Proteínas de Choque Térmico HSP72/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Estresse Fisiológico/metabolismo , Adrenalectomia , Hormônio Adrenocorticotrópico/metabolismo , Animais , Catecolaminas/metabolismo , Eletrochoque , Espaço Extracelular/metabolismo , Glucocorticoides/metabolismo , Proteínas de Choque Térmico HSP72/imunologia , Hipofisectomia , Sistema Imunitário/fisiologia , Masculino , Ratos , Ratos Endogâmicos F344 , Transdução de Sinais/fisiologia , Estresse Fisiológico/imunologia , Tirosina/farmacocinéticaRESUMO
The present experiments examined the role of spinal proinflammatory cytokines [interleukin-1beta (IL-1)] and chemokines (fractalkine) in acute analgesia and in the development of analgesic tolerance, thermal hyperalgesia, and tactile allodynia in response to chronic intrathecal morphine. Chronic (5 d), but not acute (1 d), intrathecal morphine was associated with a rapid increase in proinflammatory cytokine protein and/or mRNA in dorsal spinal cord and lumbosacral CSF. To determine whether IL-1 release modulates the effects of morphine, intrathecal morphine was coadministered with intrathecal IL-1 receptor antagonist (IL-1ra). This regimen potentiated acute morphine analgesia and inhibited the development of hyperalgesia, allodynia, and analgesic tolerance. Similarly, intrathecal IL-1ra administered after the establishment of morphine tolerance reversed hyperalgesia and prevented the additional development of tolerance and allodynia. Fractalkine also appears to modulate the effects of intrathecal morphine because coadministration of morphine with intrathecal neutralizing antibody against the fractalkine receptor (CX3CR1) potentiated acute morphine analgesia and attenuated the development of tolerance, hyperalgesia, and allodynia. Fractalkine may be exerting these effects via IL-1 because fractalkine (CX3CL1) induced the release of IL-1 from acutely isolated dorsal spinal cord in vitro. Finally, gene therapy with an adenoviral vector encoding for the release of the anti-inflammatory cytokine IL-10 also potentiated acute morphine analgesia and attenuated the development of tolerance, hyperalgesia, and allodynia. Taken together, these results suggest that IL-1 and fractalkine are endogenous regulators of morphine analgesia and are involved in the increases in pain sensitivity that occur after chronic opiates.
Assuntos
Analgésicos Opioides/farmacologia , Quimiocinas CX3C/fisiologia , Hiperalgesia/imunologia , Interleucina-1/fisiologia , Proteínas de Membrana/fisiologia , Morfina/farmacologia , Analgésicos Opioides/administração & dosagem , Animais , Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , Quimiocinas CX3C/farmacologia , Tolerância a Medicamentos , Terapia Genética , Temperatura Alta , Hiperalgesia/terapia , Inflamação/imunologia , Injeções Espinhais , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/biossíntese , Interleucina-1/líquido cefalorraquidiano , Interleucina-10/genética , Masculino , Proteínas de Membrana/farmacologia , Morfina/administração & dosagem , Dor/imunologia , Manejo da Dor , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Citocinas/antagonistas & inibidores , Receptores de HIV/antagonistas & inibidores , Sialoglicoproteínas/administração & dosagem , Sialoglicoproteínas/farmacologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologiaRESUMO
It has become clear that spinal cord glia (microglia and astrocytes) importantly contribute to the creation of exaggerated pain responses. One model used to study this is peri-spinal (intrathecal, i.t.) administration of gp120, an envelope protein of HIV-1 known to activate glia. Previous studies demonstrated that i.t. gp120 produces pain facilitation via the release of glial proinflammatory cytokines. The present series of studies tested whether spinal nitric oxide (NO) contributes to i.t. gp120-induced mechanical allodynia and, if so, what effect NO has on spinal proinflammatory cytokines. gp120 stimulation of acutely isolated lumbar dorsal spinal cords released NO as well as proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta (IL1), interleukin-6 (IL6)), thus identifying NO as a candidate mediator of gp120-induced behavioral effects. Behaviorally, identical effects were observed when gp120-induced mechanical allodynia was challenged by i.t. pre-treatment with either a broad-spectrum nitric oxide synthase (NOS) inhibitor (L-NAME) or 7-NINA, a selective inhibitor of NOS type-I (nNOS). Both abolished gp120-induced mechanical allodynia. While the literature pre-dominantly documents that proinflammatory cytokines stimulate the production of NO rather than the reverse, here we show that gp120-induced NO increases proinflammatory cytokine mRNA levels (RT-PCR) and both protein expression and protein release (serial ELISA). Furthermore, gp120 increases mRNA for IL1 converting enzyme and matrix metalloproteinase-9, enzymes responsible for activation and release of proinflammatory cytokines.
Assuntos
Citocinas/fisiologia , Proteína gp120 do Envelope de HIV/farmacologia , Mediadores da Inflamação/fisiologia , Óxido Nítrico Sintase/metabolismo , Dor/enzimologia , Animais , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Masculino , Óxido Nítrico Sintase/fisiologia , Óxido Nítrico Sintase Tipo I , Dor/virologia , Ratos , Ratos Sprague-DawleyRESUMO
Heat-shock proteins (Hsp) play an important role in stress physiology. Exposure to a variety of stressors will induce intracellular Hsp72, and this induction is believed to be beneficial for cell survival. In contrast, Hsp72 released during stress (extracellular Hsp72; eHsp72) activates pro-inflammatory responses. Clearly, physical stressors such as heat, cold, H(2)O(2), intense exercise and tail shock will induce both intra- and extracellular Hsp72. The current study tested whether a psychological stressor, cat exposure, would also trigger this response. In addition, the potential role of adrenal hormones in the Hsp72 response was examined. Adult, male Sprague Dawley rats were either adrenalectomized (ADX) or sham operated. Ten days post-recovery, rats were exposed to either a cat with no physical contact or control procedures (n = 5-6/group) for 2 h. Levels of intracellular Hsp72 were measured in the brain (frontal cortex, hippocampus, hypothalamus, dorsal vagal complex) and pituitary (ELISA). Levels of eHsp72 (ELISA) and corticosterone (RIA) were measured from serum obtained at the end of the 2-h stress period. Rats that were exposed to a cat had elevated intracellular Hsp72 in hypothalamus and dorsal vagal complex, and elevated eHsp72 and corticosterone in serum. Both the intra- and extracellular Hsp72 responses were blocked or attenuated by ADX. This study demonstrates that cat exposure can stimulate the Hsp72 response and that adrenal hormones contribute to this response.
Assuntos
Encéfalo/metabolismo , Corticosterona/sangue , Glucocorticoides/fisiologia , Proteínas de Choque Térmico/metabolismo , Estresse Psicológico/metabolismo , Corticosteroides/sangue , Corticosteroides/fisiologia , Adrenalectomia , Análise de Variância , Animais , Gatos , Epinefrina/fisiologia , Líquido Extracelular/metabolismo , Lobo Frontal/metabolismo , Proteínas de Choque Térmico HSP72 , Proteínas de Choque Térmico/sangue , Hipotálamo/metabolismo , Masculino , Hipófise/metabolismo , Comportamento Predatório/fisiologia , RatosRESUMO
Serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) are implicated in mediating learned helplessness (LH) behaviors, such as poor escape responding and expression of exaggerated conditioned fear, induced by acute exposure to uncontrollable stress. DRN 5-HT neurons are hyperactive during uncontrollable stress, resulting in desensitization of 5-HT type 1A (5-HT1A) inhibitory autoreceptors in the DRN. 5-HT1A autoreceptor downregulation is thought to induce transient sensitization of DRN 5-HT neurons, resulting in excessive 5-HT activity in brain areas that control the expression of learned helplessness behaviors. Habitual physical activity has antidepressant/anxiolytic properties and results in dramatic alterations in physiological stress responses, but the neurochemical mediators of these effects are unknown. The current study determined the effects of 6 weeks of voluntary freewheel running on LH behaviors, uncontrollable stress-induced activity of DRN 5-HT neurons, and basal expression of DRN 5-HT1A autoreceptor mRNA. Freewheel running prevented the shuttle box escape deficit and the exaggerated conditioned fear that is induced by uncontrollable tail shock in sedentary rats. Furthermore, double c-Fos/5-HT immunohistochemistry revealed that physical activity attenuated tail shock-induced activity of 5-HT neurons in the rostral-mid DRN. Six weeks of freewheel running also resulted in a basal increase in 5-HT1A inhibitory autoreceptor mRNA in the rostral-mid DRN. Results suggest that freewheel running prevents behavioral depression/LH and attenuates DRN 5-HT neural activity during uncontrollable stress. An increase in 5-HT1A inhibitory autoreceptor expression may contribute to the attenuation of DRN 5-HT activity and the prevention of LH in physically active rats.
Assuntos
Desamparo Aprendido , Neurônios/fisiologia , Núcleos da Rafe/citologia , Corrida , Serotonina/análise , Animais , Comportamento Animal , Peso Corporal , Depressão/metabolismo , Depressão/prevenção & controle , Medo , Masculino , Neurônios/química , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/biossíntese , Núcleos da Rafe/metabolismo , Ratos , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo , Receptores 5-HT1 de Serotonina , Estresse Fisiológico/metabolismoRESUMO
Habitual, moderate exercise is associated with improved health, including reductions in illness. These benefits may stem, in part, from immune function improvements. We have previously reported that daily wheel running increases serum and peritoneal natural IgM (nIgM) in pathogen-free Sprague-Dawely rats. B-1 cells, which primarily reside in the peritoneal cavity, produce nIgM in the absence of antigen stimulation. This study examined whether physical activity would also increase B-1 cell numbers in the peritoneal cavity, mesenteric lymph nodes, and spleen. Male, pathogen-free Fischer 344 rats were sedentary (standard cages) or physically active (running wheel access) for 6-7 wk. Peritoneal cavity, mesenteric lymph nodes, and spleen cells were taken, and the number of CD5+/CD11b+ (B-1) cells were measured by using two-color flow cytometry. The results were that physically active animals had increased numbers of CD5+/CD11b+ cells in the peritoneal cavity. In addition, physically active animals had increased serum and peritoneal nIgM, thus replicating our previous observations. These results indicate that voluntary running selectively increases the B-1 cell population, which is most likely responsible for the elevated serum and peritoneal nIgM in active rats. Because B-1 cells are important in host defense, these changes may contribute to the health benefits of exercise.
Assuntos
Linfócitos B/metabolismo , Antígenos CD11/fisiologia , Antígenos CD5/fisiologia , Imunoglobulina M/biossíntese , Condicionamento Físico Animal/fisiologia , Animais , Linfócitos B/imunologia , Peso Corporal/fisiologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Linfonodos/citologia , Contagem de Linfócitos , Masculino , Peritônio/citologia , Ratos , Ratos Endogâmicos F344 , Corrida/fisiologia , Baço/citologiaRESUMO
Extracellular heat-shock proteins (eHsp) such as those belonging to the 70-kDa family of Hsp (eg, Hsp72) have been hypothesized to act as a "danger signal" to immune cells, promote immune responses, and improve host defense. The current study tested this hypothesis. Adult male F344 rats were exposed to an acute laboratory stressor (100, 5-second, 1.6-mA inescapable tail shocks) and challenged with Escherichia coli. The number of colony-forming units (CFU) of bacteria at the site of injection, the levels of eHsp72, the immune response to eHsp72 and E. coli-derived lipopolysaccharide (LPS), and the amount of time required to recover from in vivo bacterial challenge were measured. CFUs were reduced 2, 4, and 6 hours after injection of E. coli in rats exposed to stress. Rats exposed to stress had elevated eHsp72 that was elevated rapidly (25 minutes) and remained elevated in the circulation and at the inflammatory site (2 hours after stressor termination). Both stressor exposure and eHsp72 administration in the absence of stress resulted in a facilitated pattern of recovery after bacterial inflammation induced by subcutaneous E. coli injection. Rats exposed to acute restraint (100 minutes) did not demonstrate elevated circulating eHsp72 or a facilitated pattern of recovery after bacterial challenge. In vitro stimulation of rat splenocytes and macrophages with eHsp72 elevated nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, and this effect was specific to eHsp72 because it was not diminished by polymyxin B and was reduced by earlier heat-denature treatment. Stimulation of cells with eHsp72 combined with LPS resulted in a greater NO and cytokine response than that observed after stimulation with eHsp72 or LPS alone. In vivo, at the inflammatory site, the bacterial-induced NO response was potentiated by stress, and NO inhibition (L-NIO) reduced the stress-induced facilitation but had no effect on the control kinetics of bacterial inflammation recovery. Thus, these results lend support to the hypothesis that intense stressor exposure increases eHsp72, which acts as a danger signal to potentiate the NO response to bacterial challenge and facilitate recovery from bacterial inflammation.