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1.
Biomed Res Int ; 2019: 8740674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380440

RESUMO

Music exposure is known to play a positive role in learning and memory and can be a complementary treatment for anxiety and fear. However, whether juvenile music exposure affects adult behavior is not known. Two-week-old Sprague-Dawley rats were exposed to music for 2 hours daily or to background noise (controls) for a period of 3 weeks. At 60 days of age, rats were subjected to auditory fear conditioning, fear extinction training, and anxiety-like behavior assessments or to anterior cingulate cortex (ACC) brain-derived neurotrophic factor (BDNF) assays. We found that the music-exposed rats showed significantly less freezing behaviors during fear extinction training and spent more time in the open arm of the elevated plus maze after fear conditioning when compared with the control rats. Moreover, the BDNF levels in the ACC in the music group were significantly higher than those of the controls with the fear conditioning session. This result suggests that music exposure in juvenile rats decreases anxiety-like behaviors, facilitates fear extinction, and increases BDNF levels in the ACC in adulthood after a stressful event.


Assuntos
Ansiedade/terapia , Musicoterapia , Música , Transtornos Fóbicos/terapia , Animais , Ansiedade/fisiopatologia , Modelos Animais de Doenças , Medo/fisiologia , Humanos , Memória/fisiologia , Transtornos Fóbicos/fisiopatologia , Ratos , Ratos Sprague-Dawley
2.
Brain Res Bull ; 149: 184-193, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31034944

RESUMO

Stress can influence decision-making in humans from many cognitive perspectives, while the underlying neurobiological mechanism remains incompletely understood. Food-foraging is a rodent behavior involving strategic possessing of nutritional supply in social context; experimental model of this behavior could help explore the effect of stress on decision-making and the brain mechanism thereof. In the present study, the influence of stress on food-foraging behavior was assessed in rats using an open field choosing paradigm wherein food collection (standard food or sweet food) were associated with social competition (with or without a rat in the cage). Acute restraint stress (ARS) was induced by placing the rat in a plastic restrainer for 2 h before food-foraging behavioral tests, with the effect of stress also determined biochemically and immunohistochemically. Restraint stressed rats showed anxiety-like behavior and elevation of serum corticosterone (CORT) and epinephrine (EPI) relative to controls. Both restraint and control animals preferred sugared food. However, the former group tended to forage food from a cage not occupied by a conspecific rat, whereas the control rats preferred to obtain food from the cage with a social competitor. Thus, the total amount of food foraged and eaten are reduced in the restrained rats than in controls. While the restraint animals had normal social interaction with other rats, they displayed enhanced social agonistic behavior. In brain examination, ARS attenuated the increase in immunolabeling and protein levels of c-fos, p-CREB, p-ERK1/2 in the anterior cingulate cortex (ACC) observed in control animals in association with food-foraging. These results indicate that restraint stressed rats tend to forage food by taking the advantage of a less competitive opportunity. Mechanistically, this decision-making alternative appears to be mediated through a neuronal deactivation in the ACC. The current findings provide novel insights into neuronal processing of decision-making behavior under the influence of stress.

3.
Sensors (Basel) ; 19(5)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30832236

RESUMO

Dynamic interaction seriously limits the overall performance of a Dual-Stage Actuator (DSA) system. This paper aims to identify and compensate for the dynamic interaction in a non-contact DSA system. The effects of the interaction in the non-contact DSA system are initially classified as non-contact position-dependent disturbance forces (PDDFs) and velocity-dependent disturbance forces (VDDFs). The PDDFs in the three degrees of freedom (DoFs) motion space between the two stages of the DSA system are directly identified in the time domain, and VDDFs are indirectly identified in the form of damping values in frequency domains. The feedforward networks of the force are subsequently applied to compensate the PDDFs and VDDFs, which are indexed with relative displacement and velocity, respectively. Experiments are finally conducted to investigate the effectiveness of compensation, which infers that the final positioning error in the time domain can be reduced from 260 nm to 130 nm with PDDFs and VDDFs compensation. The gain of the interaction transfer is decreased in the frequency range of up to 45 Hz with PDDFs and VDDFs compensation. With this method, some weak dynamic interaction can be completely compensated for by the force feedforward compensation, and the positioning accuracy of non-contact DSA systems can be greatly improved.

4.
Neurotox Res ; 35(1): 160-172, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30120712

RESUMO

Stress plays a crucial role in several psychiatric disorders, including anxiety. However, the underlying mechanisms remain poorly understood. Here, we used acute stress (AS) and chronic restraint stress (CRS) models to develop anxiety-like behavior and investigate the role of miR-150 in the hippocampi of mice. Corticosterone levels as well as glutamate receptors in the hippocampus were evaluated. We found that anxiety-like behavior was induced after either AS or CRS, as determined by the open-field test (OFT) and elevated plus-maze test (EPM). Increased corticosterone levels were observed in the blood of AS and CRS groups, while the expression of miR-150 mRNA in the hippocampus was significantly decreased. The expressions of GluN2A, GluR1, GluR2, and V-Glut2 in the hippocampus were decreased after either AS or CRS. Hippocampal GAD67 expression was increased by AS but not CRS, and GluN2B expression was decreased by CRS but not AS. Adult miR-150 knockout mice showed anxiety-like behavior, as assessed by the OFT and EPM. The expressions of GluN2A, GluN2B, GluR1, and GluR2 were also downregulated, but the expression of V-Glut2 was upregulated in the hippocampi of miR-150 knockout mice compared with wild-type mice. Interestingly, we found that the miR-150 knockout mice showed decreased dendrite lengths, dendrite branchings, and numbers of dendrite spines in the hippocampus compared with wild-type mice. These results suggest that miR-150 may influence the synaptic plasticity of the hippocampus and play a significant role in stress-induced anxiety-like behavior in adult mice.


Assuntos
Ansiedade/etiologia , Ansiedade/metabolismo , MicroRNAs/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Ansiedade/patologia , Corticosterona/metabolismo , Dendritos/metabolismo , Dendritos/patologia , Regulação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Receptores de Glutamato/metabolismo , Restrição Física , Estresse Psicológico/patologia
5.
Front Neurosci ; 12: 465, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050402

RESUMO

MiR-150 regulates maturation and differentiation of T cells but how it functions in multiple sclerosis (MS) is unclear. In miR-150 knockout (KO) mice, we examined the effect of miR-150 deletion on disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. After deleting miR-150, EAE disease severity was reduced according to clinical score. Histological staining and MBP immunofluorescence staining revealed that miR-150 deletion limited the extent of inflammatory demyelination and axonal damage in the spinal cord. Flow cytometry showed that CD3+, CD4+, and CD8+ T cells were increased in WT-EAE mice, but miR-150 deletion significantly reversed EAE-mediated up-regulation of CD3+, CD4+, and CD8+ T cells and down-regulation of CD19+ B cells. In addition, miR-150 deletion reduced the mRNA expression of IL-1ß, IL-6, IL-17, and TNF-α in spleen and spinal cord after EAE induction. Thus, miR-150 deletion reduces EAE severity and demyelination, probably through inhibiting the activated immune response and the inflammation in the central nervous system.

6.
Front Psychiatry ; 9: 776, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30740068

RESUMO

Depression and anxiety are two affective disorders that greatly threaten the mental health of a large population worldwide. Previous studies have shown that brain-derived neurotrophic factor precursor (proBDNF) is involved in the development of depression. However, it is still elusive whether proBDNF is involved in anxiety, and if so, which brain regions of proBDNF regulate these two affective disorders. The present study aims to investigate the role of proBDNF in the hippocampus in the development of depression and anxiety. Rat models of an anxiety-like phenotype and depression-like phenotype were established by complete Freund's adjuvant intra-plantar injection and chronic restraint stress, respectively. Both rat models developed anxiety-like behaviors as determined by the open field test and elevated plus maze test. However, only rats with depression-like phenotype displayed the lower sucrose consumption in the sucrose preference test and a longer immobility time in the forced swimming test. Sholl analysis showed that the dendritic arborization of granule cells in the hippocampus was decreased in rats with depression-like phenotype but was not changed in rats with anxiety-like phenotype. In addition, synaptophysin was downregulated in the rats with depression-like phenotype but upregulated in the rats with anxiety-like phenotype. In both models, proBDNF was greatly increased in the hippocampus. Intra-hippocampal injection anti-proBDNF antibody greatly ameliorated the anxiety-like and depressive behaviors in the rats. These findings suggest that despite some behavioral and morphological differences between depression and anxiety, hippocampal proBDNF is a common mediator to regulate these two mental disorders.

7.
Brain Behav ; 7(10): e00768, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29075556

RESUMO

INTRODUCTION: Decision making as a complex cognitive process involves assessing risk, reward, and costs. Typically, it has been studied in nonsocial contexts. We have developed a novel laboratory model used with rodents to detect food-foraging decision-making strategies in different social settings. However, the brain regions that mediate these behaviors are not well identified. Substantial evidence shows that the anterior cingulate cortex (ACC) participates in evaluation of social information and in decision making. METHODS: In this study, we investigated the effect of bilateral lesions in the ACC on established behaviors. Kainic acid (KA) was administered bilaterally to induce ACC lesions, and saline microinjection into the ACC was used in the sham group. RESULTS: In contrast to the sham-lesioned animals, when faced with the choice of foraging under a social context, rats with ACC lesions preferred foraging for the less desirable food. Moreover, in these situations, the total amount of food foraged by the ACC-lesioned group was less than the amount foraged by the sham group. Notably, neither social interactions nor social agonistic behaviors were affected by ACC lesions. CONCLUSIONS: These data suggest that the ACC is a key region underlying neural processing of social decision-making, specifically tending to compete for foraging high predictive reward food.


Assuntos
Tomada de Decisões/fisiologia , Giro do Cíngulo , Comportamento Social , Animais , Comportamento Animal/fisiologia , Comportamento Alimentar/psicologia , Giro do Cíngulo/metabolismo , Giro do Cíngulo/patologia , Ácido Caínico/farmacologia , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley
8.
Psychopharmacology (Berl) ; 234(22): 3321-3334, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28828505

RESUMO

RATIONALE: Environmental enrichment (EE) could influence brain plasticity and behavior in rodents. Whether the early EE may predispose individuals to a particular social hierarchy in the social dominance tube test (SDTT) at adulthood is still unknown. OBJECTIVE: The present study directly investigated the influence of EE on competitive success in the SDTT among adult rats. METHODS: Male rats were maintained in EE from postnatal days 21 to 35. Social dominance behavior was determined by SDTT, competitive food foraging test, and mate preference test at adulthood. IBA-1 expression in the hypothalamus was examined using immunohistochemistry and western blot. RESULTS: EE rats were prone to become submissive during a social encounter with standard environment (SE) rats in the SDTT. No difference was found in food foraging in the competitive food foraging test between SE and EE rats. Male EE rats were more attractive than the SE to the female rats in the mate preference test. IBA-1 expression was found to be decreased in the hypothalamus of EE rats compared to SE group. Infusion of a microglia inhibitor reduced percentage of forward in SE rats in the SDTT. Infusion of DNA methyltransferase inhibitor prevented the development of subordinate status in EE rats and restored the expression of IBA-1 in the hypothalamus. CONCLUSIONS: The results suggest that early EE did not lead to reduced social hierarchy in the male rat. However, EE caused a reduction in the percentage of forward in the SDTT, which might be associated with reduced number of microglia in the hypothalamus.


Assuntos
Predomínio Social , Meio Social , Animais , Animais Recém-Nascidos , Western Blotting , Proteínas de Ligação ao Cálcio/metabolismo , Comportamento Competitivo , Feminino , Hierarquia Social , Hipotálamo/fisiologia , Imuno-Histoquímica , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/fisiologia , Ratos , Ratos Sprague-Dawley , Comportamento Social
9.
Front Neuroanat ; 11: 45, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28638323

RESUMO

Genetic variations in the vacuolar protein sorting 10 protein (Vps10p) family have been linked to Alzheimer's disease (AD). Here we demonstrate deposition of fragments from the Vps10p member sortilin at senile plaques (SPs) in aged and AD human cerebrum. Sortilin changes were characterized in postmortem brains with antibodies against the extracellular and intracellular C-terminal domains. The two antibodies exhibited identical labeling in normal human cerebrum, occurring in the somata and dendrites of cortical and hippocampal neurons. The C-terminal antibody also marked extracellular lesions in some aged and all AD cases, appearing as isolated fibrils, mini-plaques, dense-packing or circular mature-looking plaques. Sortilin and ß-amyloid (Aß) deposition were correlated overtly in a region/lamina- and case-dependent manner as analyzed in the temporal lobe structures, with co-localized immunofluorescence seen at individual SPs. However, sortilin deposition rarely occurred around the pia, at vascular wall or in areas with typical diffuse Aß deposition, with the labeling not enhanced by section pretreatment with heating or formic acid. Levels of a major sortilin fragment ~15 kDa, predicted to derive from the C-terminal region, were dramatically elevated in AD relative to control cortical lysates. Thus, sortilin fragments are a prominent constituent of the extracellularly deposited protein products at SPs in human cerebrum.

10.
Neurotox Res ; 31(4): 505-520, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28092020

RESUMO

Early-life stress is a potent risk factor for development of psychiatric conditions such as depression. The underlying mechanisms remain poorly understood. Here, we used the early-life social isolation (ESI) model of early-life stress in rats to characterize development of depressive-like behavior, the role of microglia, levels of histone methylation, as well as expression of glutamate receptor subunits in the hippocampus. We found that depressive-like behavior was induced after ESI as determined by sucrose preference and forced swimming tests. Increased expression of microglial activation marker, Iba1, was observed in the hippocampus of the ESI group, while expression of the microglial CD200 receptor, which promotes microglial quiescence, significantly decreased. In addition, increased levels of proinflammatory cytokines, interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were observed in the hippocampus of the ESI group. Moreover, ESI increased levels of neuronal H3K9me2 (a repressive marker of transcription) and its associated "writer" enzymes, G9a and G9a-like protein, in the hippocampus. ESI also decreased expression of hippocampal NMDA receptor subunits, NR1, and AMPA receptor subunits, GluR1 and GluR2, which are involved in synaptic plasticity, but it did not affect expression of PSD95 and NR2B. Interestingly, treatment with minocycline to block microglial activation induced by ESI inhibited increases in hippocampal microglia and prevented ESI-induced depressive-like behavior as well as increases in IL-1ß, IL-6, and TNF-α. Notably, minocycline also triggered downregulation of H3K9me2 expression and restored expression of NR1, GluR1, and GluR2. These results suggest that ESI induces depressive-like behavior, which may be mediated by microglial signaling.


Assuntos
Depressão/metabolismo , Histonas/metabolismo , Microglia/metabolismo , Minociclina/farmacologia , Isolamento Social/psicologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large , Preferências Alimentares/efeitos dos fármacos , Hipocampo/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Resposta de Imobilidade Tônica/efeitos dos fármacos , Interleucina-1beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Metilação/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Ratos , Receptores de AMPA/metabolismo , Receptores Imunológicos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
11.
Onco Targets Ther ; 9: 6999-7009, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27895492

RESUMO

MicroRNA (miR)-29a has been implicated in non-small cell lung cancer (NSCLC), but the mechanism remains largely unclear. LASP1, a cAMP- and cGMP-dependent signaling protein, was recently found to promote proliferation and aggressiveness in NSCLC. However, the regulatory mechanism of LASP1 expression in NSCLC, as well as the relationship between LASP1 and miR-29a, has never been previously studied. In this study, we found that miR-29a was remarkably downregulated and low expression of miR-29a was associated with the malignant progression of NSCLC. Moreover, the expression of LASP1 was markedly increased in NSCLC tissues and cell lines. Bioinformatics analysis and luciferase reporter assay data further identified LASP1 as a target gene of miR-29a, and the expression of LASP1 was negatively mediated by miR-29a at the post-transcriptional level in NSCLC cells. Overexpression of miR-29a reduced the proliferation, migration, and invasion of NSCLC cells, just as the effects of LASP1 knockdown. Moreover, overexpression of LASP1 attenuated the suppressive effect of miR-29a on the malignant phenotypes of NSCLC cells. In addition, upregulation of miR-29a decreased the growth of A549 cells in nude mice and protected the animals from tumor-induced death. Therefore, we demonstrate that miR-29a plays a suppressive role in NSCLC via targeting LASP1, suggesting that the miR-29a/LASP1 axis may become a promising therapeutic target for NSCLC.

12.
Int J Cardiol ; 220: 454-61, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27390969

RESUMO

BACKGROUND: Hypothermia reduces immediate paralysis during surgical repair of aortic aneurysms. However, it is unknown what the impact of hypothermia is on delayed paralysis, a serious complication of this type of surgery. METHODS: Sprague-Dawley rats were subjected to occlusion of the descending aorta at different duration under normothermia (38.0±0.5) or hypothermia (33.0±0.5°). Neurologic function was assessed. Motor neuron number, glial activation, and cytokine expression in the spinal cord were examined. Minocycline was administered perioperatively by intraperitoneal injection in the rats subjected to the aorta occlusion. RESULTS: In contrast to normothermia conditions at which immediate paralysis occurred when the duration of aorta occlusion exceeded 11.5min, hypothermia did not induce immediate paralysis if the duration of aorta occlusion was less than 41min. However, delayed paralysis was developed when the duration of aorta occlusion exceeded 18min, and reached peak level when the duration of aorta occlusion was 40min at hypothermia condition. The number of motoneurons was significantly decreased (P<0.05) at 30h postoperation. In addition, microglia was activated, and interleukin-1ß and interleukin-6 levels were upregulated, both of which were co-localized in microglia at 24h postoperation in the hypothermia group. Minocycline treatment attenuated the incidence and degree of paralysis but did not decrease the mortality. CONCLUSIONS: Hypothermia, a neuroprotective strategy in cardiothoracic surgery, increased the incidence of delayed paralysis through activation of spinal microglia and cytokines. Blocking the activated microglia may be a potential intervention to prevent the incidence of delayed paralysis.


Assuntos
Aorta Torácica/metabolismo , Aneurisma Aórtico/metabolismo , Hipotermia Induzida/métodos , Microglia/metabolismo , Paralisia/metabolismo , Medula Espinal/metabolismo , Animais , Aneurisma Aórtico/patologia , Modelos Animais de Doenças , Incidência , Masculino , Paralisia/patologia , Paralisia/prevenção & controle , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
13.
Sci Rep ; 6: 27171, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27251195

RESUMO

The precursor of brain derived neurotrophic factor (proBDNF), the unprocessed BDNF gene product, binds to its receptors and exerts the opposing biologic functions of mature BDNF. proBDNF is expressed in the peripheral tissues but the functions of peripheral proBDNF remain elusive. Here we showed that proBDNF and its predominant receptor, p75 pan-neurotrophin receptor were upregulated in the nerve fibers and inflammatory cells in the local tissue in inflammatory pain. Neutralization of proBDNF by polyclonal antibody attenuated pain in different models of inflammatory pain. Unilateral intra-plantar supplementation of proBDNF by injecting exogenous proBDNF or ectopic overexpression resulted in pain hypersensitivity and induced spinal phosphorylated extracellular signal-regulated kinase activation. Exogenous proBDNF injection induced the infiltration of inflammatory cells and the activation of proinflammatory cytokines, suggesting that inflammatory reaction contributed to the pro-algesic effect of proBDNF. Finally, we generated monoclonal anti-proBDNF antibody that could biologically block proBDNF. Administration of monoclonal Ab-proBDNF attenuated various types of inflammatory pain and surgical pain. Thus, peripheral proBDNF is a potential pain mediator and anti-proBDNF pretreatment may alleviate the development of inflammatory pain.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Mediadores da Inflamação/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Dor/imunologia , Receptores de Fator de Crescimento Neural/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Células Cultivadas , Citocinas/farmacologia , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Masculino , Camundongos , Proteínas do Tecido Nervoso/genética , Dor/etiologia , Dor/genética , Dor/metabolismo , Fosforilação , Ratos , Receptores de Fator de Crescimento Neural/genética , Regulação para Cima
14.
Neurosci Lett ; 624: 34-41, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27132084

RESUMO

Psychological stress affects human health, and chronic stress leads to life-threatening diseases, such as depression and post-traumatic stress disorder. Psychological stress coping mechanisms involve the brain-derived neurotrophic factor (BDNF) and downstream cAMP response element binding protein (CREB), which are targets of the adverse effects of stress paradigms. Fourty-seven adult male Sprague-Dawley rats were divided into control, physical stress and six psychological stress groups which were assayed at 0h, 0.5h, 1h, 2h, 6h and 24h after communication box (CB) stress induction. Behavioral assessment using open field and elevated plus maze tests determined that CB stress significantly increased anxiety. After CB stress, the alternation of mRNA levels of BDNF and CREB were assessed at different time points by in situ hybridization. The mRNA levels of BDNF and CREB were significantly decreased, then gradually recovered over 24h to maximum levels in the hippocampus (CA1 region), prefrontal cortex (PFC), central amygdaloid nuclei (AG), shell of accumbens nucleus (NAC), periaqueductal gray (PAG) and ventral tegmental area, except for the ventral tegmental area (VTA). Moreover, mRNA levels of BDNF and CREB were positively correlated in all examined brain regions, except for the VTA region at 0 and 24h after CB stress induction. These findings suggest that BDNF and CREB may belong to the same pathway and be involved in psychological stress response mechanisms, and protect the organism from stress induced, aversive processes leading to disease.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Estresse Psicológico/metabolismo , Animais , Ansiedade/etiologia , Ansiedade/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/complicações
15.
BMC Neurosci ; 17: 3, 2016 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-26754043

RESUMO

BACKGROUND: In highly complex social settings, an animal's motivational drive to pursue an object depends not only on the intrinsic properties of the object, but also on whether the decision-making animal perceives an object as being the most desirable among others. Mimetic desire refers to a subject's preference for objects already possessed by another subject. To date, there are no appropriate animal models for studying whether mimetic desire is at play in guiding the decision-making process. Furthermore, the neuropharmacological bases of decision-making processes are not well understood. In this study, we used an animal model (rat) to investigate a novel food-foraging paradigm for decision-making, with or without a mimetic desire paradigm. RESULTS: Faced with the choice of foraging in a competitive environment, rats preferred foraging for the desirable object, indicating the rats' ability for decision-making. Notably, treatment with the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, but not with the dopamine D1 or D2 receptor antagonists, SCH23390 and haloperidol, respectively, suppressed the food foraging preference when there was a competing resident rat in the cage. None of these three antagonists affected the food-foraging preference for palatable food. Moreover, MK-801 and SCH23390, but not haloperidol, were able to abolish the desirable environment effect on standard food-foraging activities in complex social settings. CONCLUSIONS: These results highlight the concept that mimetic desire exerts a powerful influence on food-foraging decision-making in rats and, further, illustrate the various roles of the glutamatergic and dopaminergic systems in mediating these processes.


Assuntos
Comportamento Competitivo/fisiologia , Tomada de Decisões/fisiologia , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Animais , Benzazepinas/administração & dosagem , Comportamento Competitivo/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Maleato de Dizocilpina/administração & dosagem , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Preferências Alimentares/efeitos dos fármacos , Preferências Alimentares/fisiologia , Haloperidol/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
16.
Psychopharmacology (Berl) ; 232(24): 4433-44, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26400403

RESUMO

RATIONALE: Pain-related anxiety and depression are well known to be comorbid with chronic pain and adversely affect patient quality of life. Recent studies have shown that anxiety-like behaviors also develop with acute surgical pain, but the effects of general anesthetics on acute pain-related anxiety are unknown. OBJECTIVE: The present study aimed to compare the effects of different general anesthetics on anxiety-like behaviors that follow formalin-induced acute pain in a rat model. METHODS: Formalin-induced acute inflammatory pain was established by intraplantar injection of 1% formalin without anesthesia or with anesthesia using the clinical anesthetics sevoflurane, propofol, or pentobarbital sodium. Anxiety-like behaviors were studied using the open-field test and elevated plus maze. Phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 expression in the anterior cingulate cortex (ACC) and spinal cord was examined using immunohistochemistry. RESULTS: Anxiety-like behaviors were observed at 24 and 72 h post-formalin injection. Concomitantly, p-ERK 1/2 expression was upregulated in the ACC at 1 and 24 h post-formalin injection. While all three general anesthetics effectively blocked nociceptive responses and activation of ERK in the rat ACC following formalin injection during anesthesia, only sevoflurane inhibited ERK activation in the spinal cord and ACC at 24 h post-injection. CONCLUSIONS: This study suggests that sevoflurane, but not intravenous anesthetics, inhibits pain-related anxiety, along with ERK activation in the ACC, probably through inhibition of spinal nociceptive transmission. Intraoperative application of inhaled anesthetics may be a better choice to reduce postoperative anxiety.


Assuntos
Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Giro do Cíngulo/metabolismo , Dor/metabolismo , Anestésicos Inalatórios , Animais , Formaldeído , Masculino , Éteres Metílicos/farmacologia , Dor/induzido quimicamente , Medição da Dor , Pentobarbital/farmacologia , Propofol/farmacologia , Ratos , Ratos Sprague-Dawley , Sevoflurano , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo
17.
BMC Neurosci ; 16: 14, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25884414

RESUMO

BACKGROUND: Neuropathic pain evoked by nerve injury is frequently accompanied by deterioration of emotional behaviors, but the underlying signaling mechanisms remain elusive. Glutamate (Glu) is the major mediator of excitatory synaptic transmission throughout the brain, and abnormal activity of the glutamatergic system has been implicated in the pathophysiology of pain and associated emotional comorbidities. In this study we used the partial sciatic nerve ligation (PSNL) model of neuropathic pain in rats to characterize the development of anxiety-like behavior, the expression of glutamatergic receptors, and the phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, the region that encodes memories related to emotions. RESULTS: We found that the mechanical withdrawal threshold was significantly reduced and an anxiety-like behavior was increased as determined via open field tests and elevated plus-maze tests at 28 days after injury. No significant differences were found in the ratio of sucrose preference and immobility time detected by sucrose preference tests and forced swimming tests respectively, possibly due to the timing factor. The expression of N-methyl-D-aspartate (NMDA) receptor subtypes NR1 and NR2B, but not NR2A, GluR1, or GluR2 (the main subtype of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] receptor) in the hippocampus of injured rats was significantly reduced. Moreover, PSNL resulted in decreased phosphorylation of ERK1/2 in the hippocampus. Intriguingly, treatment with D-serine (a co-agonist of NMDA receptor, 1 g/kg intraperitoneally) reduced the anxiety-like behavior but not the mechanical hypersensitivity induced by PSNL. CONCLUSIONS: PSNL can induce significant anxiety-like but not depression-like behavior, and trigger down-regulation of NMDA but not AMPA receptors in the hippocampus at 28 days after injury.


Assuntos
Ansiedade/fisiopatologia , Hipocampo/metabolismo , Neuralgia/fisiopatologia , Receptores de Glutamato/metabolismo , Neuropatia Ciática/fisiopatologia , Anedonia/efeitos dos fármacos , Anedonia/fisiologia , Animais , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Sacarose na Dieta/administração & dosagem , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/fisiopatologia , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Neuralgia/complicações , Neuralgia/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Nervo Isquiático/fisiopatologia , Neuropatia Ciática/complicações , Neuropatia Ciática/tratamento farmacológico , Serina/farmacologia
18.
Exp Ther Med ; 9(4): 1351-1356, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25780434

RESUMO

Oxytocin (OT) neurons localized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) send fibers to the brain and spinal cord. While most previous studies have looked at the role of OT in chronic pain, few have investigated the role of OT in acute pain, particularly postoperative pain. In the present study, the role of OT in incision-induced allodynia was explored for the first time, using a rat incisional pain model. Immunohistochemical staining showed that, compared with the baseline (prior to incision) measurements, the OT content in the PVN was significantly decreased at 0.5, 1.0 and 3.0 h post-incision and returned to the baseline level at 6.0 h post-incision. By contrast, there was no significant difference in the OT content in the SON prior to and subsequent to incision. A dose-dependent inhibition of mechanical hypersensitivity was detected 30 min after intracerebroventricular injection of OT (100, 400 or 600 ng) and lasted for 3.0 h. No significant difference was noted, however, between the intrathecal OT injection group (600 ng) and the control group. In conclusion, the present study provides the first in vivo evidence that OT in the PVN predominantly attenuates incision-induced mechanical allodynia at the supraspinal, rather than the spinal, level. This suggests that OT is involved in supraspinal analgesia for postoperative pain.

19.
Behav Brain Res ; 286: 1-10, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25721744

RESUMO

BRD7 is a bromodomain-containing protein (BCP), and recent evidence implicates the role of BCPs in the initiation and development of neurodevelopmental disorders. However, few studies have investigated the biological functions of BRD7 in the central nervous system. In our study, BRD7 was found to be widely expressed in various regions of the mouse brain, including the medial prefrontal cortex (mPFC), caudate putamen (CPu), hippocampus (Hip), midbrain (Mb), cerebellum (Cb), and mainly co-localized with neuron but not with glia. Using a BRD7 knockout mouse model and a battery of behavioral tests, we report that disruption of BRD7 results in impaired cognitive behavior leaving the emotional behavior unaffected. Moreover, a series of proteins involved in synaptic plasticity were decreased in the medial prefrontal cortex and there was a concomitant decrease in neuronal spine density and dendritic branching in the medial prefrontal cortex. However, no significant difference was found in the hippocampus compared to the wild-type mice. Thus, BRD7 might play a critical role in the regulation of synaptic plasticity and affect cognitive behavior.


Assuntos
Proteínas Cromossômicas não Histona/deficiência , Transtornos Cognitivos/fisiopatologia , Plasticidade Neuronal/fisiologia , Córtex Pré-Frontal/fisiopatologia , Animais , Ansiedade/patologia , Ansiedade/fisiopatologia , Western Blotting , Proteínas Cromossômicas não Histona/genética , Transtornos Cognitivos/patologia , Dendritos/patologia , Dendritos/fisiologia , Depressão/patologia , Depressão/fisiopatologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Imuno-Histoquímica , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Testes Neuropsicológicos , Percepção Olfatória/fisiologia , Reconhecimento Fisiológico de Modelo/fisiologia , Córtex Pré-Frontal/patologia , Percepção Social
20.
Neuropharmacology ; 89: 318-24, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25446675

RESUMO

Depression is a common psychiatric disorder associated with chronic stress. Insulin-like growth factor 2 (IGF2) is a growth factor that serves important roles in the brain during development and at adulthood. Here, the role of IGF2 expression in the hippocampus was investigated in a rat model of depression. A chronic restraint stress (CRS) model of depression was established in rats, exhibiting depression-like behavior as assessed with the sucrose preference test (SPT) and forced swimming test (FST), and with evaluation of the corticosterone levels. Hippocampal IGF2 levels were significantly lower in rats suffering CRS than in controls, as were levels of pERK1/2 and GluR1. Lentivirus-mediated hippocampal IGF2 overexpression alleviated depressive behavior in restrained rats, elevated the levels of pERK1/2 and GluR1 proteins, but it did not affect the expression of pGSK3ß, GluR2, NMDAR1, and NMDAR2A. These results suggest the chronic restraint stress induces depressive behavior, which may be mediated by ERK-dependent IGF2 signaling, pointing to an antidepressant role for this molecular pathway.


Assuntos
Depressão/tratamento farmacológico , Depressão/etiologia , Regulação da Expressão Gênica/fisiologia , Fator de Crescimento Insulin-Like II/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/patologia , Animais , Peso Corporal/fisiologia , Doença Crônica , Corticosterona/metabolismo , Modelos Animais de Doenças , Preferências Alimentares , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Fator de Crescimento Insulin-Like II/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Sacarose/administração & dosagem , Natação/psicologia , Transdução Genética
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