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1.
PLoS One ; 19(6): e0301895, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38837940

RESUMEN

Development of autonomous vehicles (AVs) is growing in a rapid rate, however, the most dominant barriers in their adoption seem to be rather psychological than technical. The present online survey study aimed to investigate which demographical and personality dimensions predict attitudes towards AVs on a Hungarian sample (N = 328). Data was collected by convenience and snowball sampling. Three-level hierarchical regression models were applied: in the first level, demographical variables, then general personality traits and third, attitude-like personality factors were entered. We demonstrated that the predictive effect of age, gender and education disappeared when personality dimensions were included into the models. Importantly, more positive general attitudes towards technology and higher optimism regarding innovations predicted eagerness to adopt AVs. On the other hand, individuals with more negative attitudes and higher dependence on technology as well as those with lower level of Sensory Sensation Seeking and higher level of Conscientiousness were more concerned about AVs. Our results suggest that AV acceptance cannot be regarded as a one-dimensional construct and that certain personality traits might be stronger predictors of AV acceptance than demographical factors.


Asunto(s)
Personalidad , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Actitud , Hungría , Adulto Joven , Adolescente
2.
Therap Adv Gastroenterol ; 16: 17562848231214086, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38078296

RESUMEN

Background: Burnout remains a significant health concern within the healthcare sector. Numerous studies have explored burnout among gastroenterologists. However, as far as we are aware, there is currently no documented research specifically focused on burnout for specialists in the field of inflammatory bowel disease (IBD). Objective: The aim of our study was to assess the extent of burnout, its determinants, and to analyze potential risk factors among European healthcare professionals who provide care to patients with IBD. Methods: We carried out a cross-sectional pilot study involving healthcare professionals responsible for the treatment of patients with IBD. A total of 102 participants (56.9% male, average age 48 ± 10.6) completed the anonymous multiple question open web survey. The survey consisted of four distinct psychological constructs (burnout, depression, somatization, and well-being), along with inquiries associated with sociodemographic, health-related, and work-related factors. Results: In our study, we observed that 47.1% of professionals specializing in IBD experienced burnout. When considering all three factors of burnout simultaneously, 5.9% of participants fell within the moderate range. Among these, depersonalization (DP) was the most prevalent factor, with 48% at a medium level and 47.1% at a high level. Depression, somatization, and well-being correlated with emotional exhaustion (EE) and DP, while only depression correlated with personal accomplishment (PA). Furthermore, age, physical activity, total time spent in healthcare, and time spent as an IBD specialist were correlated with EE. Multiple linear regression analysis revealed that depression was the most dominant predictor of both PA and DP. In terms of work-related factors, we observed that having endoscopic access had a detrimental impact on burnout, while the presence of a dedicated IBD outpatient unit and opportunities to participate in multidisciplinary meetings had a positive effect on mitigating burnout. Conclusions: Our pilot study underscores the importance of burnout among IBD professionals in Europe, with a specific emphasis on DP. Subsequent studies may help to uncover the way underlying factors contribute to burnout, potentially laying the foundation for international support and prevention initiative programs.


Burnout among European IBD specialists Professionals working with IBD patients are at high risk of burnout. The prevalence of depersonalization is the highest and there are several other risk factors. However, we also found protective factors that may help to reduce and prevent burnout.

3.
Cogn Res Princ Implic ; 8(1): 15, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36786909

RESUMEN

The current study addressed the relationship between subjective memory complaints and negative affect, well-being, and demographic variables by investigating the Hungarian version of Multifactorial Memory Questionnaire. The original factor structure showed a poor fit on our data; therefore, principal component analysis was conducted on data from 577 participants, ranging in age from 18 to 92 years. Our analysis provided a six-component solution: Satisfaction, Retrospective memory mistakes, Prospective memory mistakes, External Strategies, Internal Strategies, and Frustration. To improve the reliability and internal consistency indicators we created four subscales by combining Frustration with Satisfaction, and Retrospective and Prospective memory mistakes subscales. Thus, we were able to preserve the factor structure similar to the original. Subjective memory complaints were correlated positively with anxiety and depression and were associated negatively with well-being. We found a slight positive correlation between age and memory ability, and age was associated negatively with the frequency of external strategy use. Individuals with higher education were satisfied with their memory, used more frequent external strategies. Furthermore, men were more satisfied with their memory and reported better memory ability, while women tended to use more external and internal strategies. Women also showed a higher level of anxiety and depression than men. In conclusion, self-reported memory changes are of particular importance because of their association with perceived mental health status and implications for later disease development.


Asunto(s)
Metacognición , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Reproducibilidad de los Resultados , Estudios Retrospectivos , Hungría , Trastornos de la Memoria/etiología , Trastornos de la Memoria/psicología , Afecto , Encuestas y Cuestionarios
4.
Heliyon ; 9(1): e12910, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36685410

RESUMEN

Cognitive Failures Questionnaire (CFQ) is a widely utilized tool to measure the frequency of everyday cognitive lapses. Here we present a validation study of the Hungarian translation of CFQ. A subsample (n = 157) filled out the questionnaire twice within a 7-21 days interval to determine test-retest reliability. Exploratory structural equation modeling (ESEM) method was run on a larger sample (n = 382) for testing a different number of potential factors. Although the multiple-factor solutions showed good fit, the one-factor solution described the data more adequately. The composite reliability of the final model (CR = .822) as well as test-retest reliability (intraclass correlation coefficient = .900) and the internal consistency (Cronbach's alpha = .920) of the CFQ were high. Higher CFQ scores (i.e., more cognitive slips) correlated positively with anxiety and depression while a negative relationship was present with well-being. Furthermore, women were characterized with higher CFQ scores compared to men. Our results are in line with previous studies, and the excellent psychometric properties make the Hungarian version of CFQ an appropriate measure of cognitive failures.

5.
Sci Rep ; 12(1): 13312, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-35922644

RESUMEN

The goal of the present study is to examine the cognitive/affective physiological correlates of passenger travel experience in autonomously driven transportation systems. We investigated the social acceptance and cognitive aspects of self-driving technology by measuring physiological responses in real-world experimental settings using eye-tracking and EEG measures simultaneously on 38 volunteers. A typical test run included human-driven (Human) and Autonomous conditions in the same vehicle, in a safe environment. In the spectrum analysis of the eye-tracking data we found significant differences in the complex patterns of eye movements: the structure of movements of different magnitudes were less variable in the Autonomous drive condition. EEG data revealed less positive affectivity in the Autonomous condition compared to the human-driven condition while arousal did not differ between the two conditions. These preliminary findings reinforced our initial hypothesis that passenger experience in human and machine navigated conditions entail different physiological and psychological correlates, and those differences are accessible using state of the art in-world measurements. These useful dimensions of passenger experience may serve as a source of information both for the improvement and design of self-navigating technology and for market-related concerns.


Asunto(s)
Conducción de Automóvil , Estatus Social , Automatización , Conducción de Automóvil/psicología , Movimientos Oculares , Humanos , Tecnología
6.
Hum Mov Sci ; 84: 102969, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35704968

RESUMEN

Ideomotor theories suggest that different action-effects are not equally important in goal-directed actions, and that task-relevant information are weighted stronger during the representation of actions. This stronger weighting of task-relevant action-effects might also enable to utilize them as retrieval cues of the corresponding motor patterns. The aim of the present study was to investigate how the consistent presence or absence of a sound action-effect influenced the retrieval of the motor components of a simple, everyday action (pinching) as reflected by the pattern of force application and surface electromyogram (sEMG) recorded from the abductor pollicis brevis (APB) and first dorsal interosseous (FDI). Participants applied pairs of pinch impulses to a force sensitive resistor (FSR). The presence or absence of a sound action-effect and the between-action interval (BAI, 2 or 4 s) were manipulated blockwise, whereas the target force level (low or high) was randomly cued from trial to trial. When actions resulted in a sound, force and sEMG activity were reduced. This effect was more pronounced for low target force level trials, which is compatible with a stronger weighting of the sound action-effect when the intensity of the tactile and proprioceptive action-effects is low. Surprisingly, the FDI activity was more variable within actions pairs in the 2 s BAI conditions, which suggests that action pairs separated by the longer time interval might have been represented differently from those separated by the shorter interval.


Asunto(s)
Gravitación , Músculo Esquelético , Electromiografía/métodos , Humanos
7.
Biol Psychol ; 159: 108024, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33460782

RESUMEN

The N1 event-related potential (ERP) enhancement to auditory transients preceded briefly by another transient has been interpreted as a reflection of latent inhibition, or alternatively, as a superimposing mismatch negativity (MMN) to rare transient event combinations. In a previous study (Volosin, Gaál, & Horváth, 2017a), when rare glides preceded frequent gaps by 150 ms in continuous tones, gap-related N1 was enhanced in younger adults while P2 was attenuated both in younger and older adults, which could be parsimoniously explained by MMN overlap which was delayed with aging. The present study replicated and extended these results with a condition in which the roles of the two event types were reversed. Transients separated by 150 ms elicited delayed MMN in older adults, supporting the MMN interpretation over the latent inhibition account. Furthermore, the divergence of N1 and MMN elicitation patterns demonstrated the independence of N1 and MMN.


Asunto(s)
Electroencefalografía , Potenciales Evocados Auditivos , Estimulación Acústica , Anciano , Percepción Auditiva , Potenciales Evocados , Humanos , Tiempo de Reacción
8.
Brain Res ; 1727: 146565, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31765629

RESUMEN

Keeping task-relevant sensory events in the focus of attention while ignoring irrelevant ones is crucial for optimizing task behavior. This attention-distraction balance might change with the perceptual demands of the ongoing task: while easy tasks might be performed with low attentional effort, difficult ones require enhanced attention. The goal of the present study was to investigate how task difficulty affected allocation of attention and distractibility in an auditory distraction paradigm. Participants performed a tone duration discrimination task in which tones were rarely, occasionally presented at a rare pitch (distracters), and task difficulty was manipulated by the duration difference between short and long tones. Short tones were consistently 200 ms long, while long tone duration was 400 ms in the easy, and 260 ms in the difficult condition. Behavioral results and deviant-minus-standard event-related potential (ERP) waveforms suggested similar magnitudes of distraction in both conditions. ERPs without such a subtraction showed that tone onsets were preceded by a negative-going trend, suggesting that participants prepared for tone onsets. In the difficult condition, N1 amplitudes to tone onsets were enhanced, indicating that participants invested more attentional resources. Increased difficulty also slowed down tone offset processing as reflected by significantly delayed offset-related P1 and N1/N2 waveforms. These results suggest that although task difficulty compels participants to attend the tones more strongly, this does not have significant impact on distraction-related processing.


Asunto(s)
Atención/fisiología , Percepción Auditiva/fisiología , Encéfalo/fisiología , Discriminación en Psicología/fisiología , Estimulación Acústica , Adulto , Electroencefalografía , Potenciales Evocados , Femenino , Humanos , Masculino , Desempeño Psicomotor , Tiempo de Reacción , Adulto Joven
9.
Front Cell Neurosci ; 13: 485, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31736712

RESUMEN

Neurotrophins activate Trk receptor signaling to support neuronal survival and many aspects of neuronal function. Early studies demonstrated that TrkA formed a complex with the p75 neurotrophin receptor (p75 NTR ), which increased the affinity and selectivity of NGF binding, however, whether interaction of p75 NTR with other Trk receptors performs a similar function to enhance ligand binding has not been demonstrated. We investigated the interaction of TrkB with full length p75 NTR in hippocampal neurons in response to BDNF and found that the association of these receptors occurs after ligand binding and requires phosphorylation of TrkB, indicating that formation of this receptor complex was not necessary for ligand binding. Moreover, the interaction of these receptors required internalization and localization to early endosomes. We found that association of TrkB with p75 NTR was necessary for optimal downstream signaling of the PI3K-Akt pathway, but not the Erk pathway, in hippocampal neurons. The absence of p75 NTR impaired the ability of BDNF to rescue hippocampal neurons in a trophic deprivation model, suggesting that p75 NTR facilitates the ability of TrkB to activate specific pathways to promote neuronal survival.

10.
eNeuro ; 5(1)2018.
Artículo en Inglés | MEDLINE | ID: mdl-29349290

RESUMEN

Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified lithium citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low, submicromolar doses of lithium citrate effectively inhibited proNGF-induced cell death in cultured neurons and protected hippocampal neurons following pilocarpine-induced SE in vivo. We analyzed specific mechanisms by which lithium citrate afforded neuroprotection and determined that lithium citrate prevented the association and internalization of the p75NTR-sortilin receptor complex. Our results demonstrate a novel mechanism by which low-dose treatments of lithium citrate are effective in attenuating p75NTR-mediated cell death in vitro and in vivo.


Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Muerte Celular/efectos de los fármacos , Citratos/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Receptores de Factor de Crecimiento Nervioso/metabolismo , Animales , Muerte Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Masculino , Neuronas/metabolismo , Neuronas/patología , Pilocarpina , Ratas , Células Sf9 , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/metabolismo , Estado Epiléptico/patología
11.
Sci Rep ; 7(1): 10143, 2017 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-28860638

RESUMEN

When background auditory events lead to enhanced auditory event-related potentials (ERPs) for closely following sounds, this is generally interpreted as a transient increase in the responsiveness of the auditory system. We measured ERPs elicited by irrelevant probes (gaps in a continuous tone) at several time-points following rare auditory events (pitch glides) in younger and older adults, who watched movies during stimulation. Fitting previous results, in younger adults, gaps elicited increasing N1 auditory ERPs with decreasing glide-gap separation. N1 increase was paralleled by an ERP decrease in the P2 interval. In older adults, only a glide-gap separation dependent P2 decrease, but no N1-effect was observable. This ERP pattern was likely caused by a fronto-central negative waveform, which was delayed in the older adult group, thus overlapping N1 and P2 in the younger, but overlapping only P2 in the older adult group. Because the waveform exhibited a polarity reversal at the mastoids, it was identified as a mismatch negativity (MMN). This interpretation also fits previous studies showing that gap-related MMN is delayed in older adults, reflecting an age-related deterioration of fine temporal auditory resolution. These results provide a plausible alternative explanation for the ERP enhancement for sounds following background auditory events.


Asunto(s)
Envejecimiento/fisiología , Potenciales Evocados Auditivos , Adolescente , Adulto , Anciano , Percepción Auditiva , Femenino , Humanos , Persona de Mediana Edad , Tiempo de Reacción
12.
Neurobiol Aging ; 57: 232-246, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28666708

RESUMEN

It has been hypothesized that age-related hearing loss is caused not only by peripheral but also central changes in the auditory system. Many studies used event-related potentials (ERPs) elicited by sound onsets to characterize the age-related differences in central auditory processing. Age-related ERP enhancements in such studies have often been interpreted in terms of elevated sensitivity to auditory stimulation. Such ERPs, however, comprise various components reflecting different aspects of auditory and task-related processing. The composition of the waveforms may considerably differ for ERPs elicited by other auditory events. In the present study, ERPs elicited by tone offsets were used to characterize processing differences between younger and older adults in a short-go, tone-duration discrimination paradigm. Whereas the onset-related auditory ERP was enhanced in the older adult group, no age-related differences were found in the offset-related auditory ERPs observable at temporal electrodes. In older adults, however, offset-related processing was dominated by an N2 that could reflect enhanced cognitive control activities. Because N2 was present regardless discrimination difficulty, younger adults may have framed the task as offset detection, whereas older adults represented the task as "genuine" discrimination.


Asunto(s)
Estimulación Acústica , Envejecimiento/fisiología , Envejecimiento/psicología , Encéfalo/fisiología , Cognición/fisiología , Potenciales Evocados Auditivos/fisiología , Potenciales Evocados/fisiología , Discriminación de la Altura Tonal/fisiología , Sonido , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción , Adulto Joven
13.
Biol Psychol ; 126: 71-81, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28411034

RESUMEN

The present study investigated how fast younger and older adults recovered from a distracted attentional state induced by rare, unpredictable sound events. The attentional state was characterized by the auditory N1 event-related potential (ERP), which is enhanced for sound events in the focus of attention. Younger (19-26 years) and older (62-74 years) adults listened to continuous tones containing rare pitch changes (glides) and short gaps. Glides and gaps could be separated in 150ms, 250ms, 650ms or longer and the task was gap detection while ignoring glides. With longer glide-gap separations similar N1 enhancements were observable in both groups suggesting that the duration of the distracted sensory state was not affected by aging. Older adults responded, however, slower at short glide-gap separations which indicated that distraction at subsequent levels of processing may have nonetheless more impact in older than in younger adults.


Asunto(s)
Estimulación Acústica/psicología , Factores de Edad , Atención/fisiología , Potenciales Evocados/fisiología , Tiempo de Reacción/fisiología , Estimulación Acústica/métodos , Adulto , Anciano , Percepción Auditiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sonido , Adulto Joven
14.
Brain Res ; 1639: 120-31, 2016 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-26947619

RESUMEN

The human cognitive system has various functions to enhance performance in tasks requiring responses to stimuli. When potentially occurring stimuli are known, we can establish selective attention sets and ignore task-irrelevant events while attending task-relevant ones. When the stimulation is temporally structured, we can rely on constant temporal relationships between stimulus events to prepare for the task-relevant moments. Most distraction paradigms feature task-irrelevant events which are followed by task-relevant ones within a constant interval, and distraction is induced by randomly replacing some of the standard task-irrelevant events. The constant time interval transforms irrelevant events to task-supportive temporal cues, which are integrated into the task-behavior by the participants. The present study investigated whether distracters could be utilized as temporal cues to support task-related processing in a continuous auditory stimulation paradigm. A continuous tone featuring short and long gaps, and pitch glides was presented. Participants performed a gap duration discrimination task, while ignoring glides. Glides could be presented frequently or rarely. In the informative condition, 80% of the glides predicted the presentation time of the forthcoming gap (400ms), while in the uninformative condition, the occurrence of gaps and glides was independent. Rare glides elicited an enhanced N1, mismatch negativity, and P3 event-related potentials in both informative and uninformative conditions. In informative conditions glides were followed by a contingent negative variation; and rare informative glides elicited an N2b, suggesting that despite triggering distraction-related processes, distracters could be integrated into the task-behavior, and could be utilized as task-supportive cues.


Asunto(s)
Anticipación Psicológica/fisiología , Atención/fisiología , Percepción Auditiva/fisiología , Encéfalo/fisiología , Percepción del Tiempo/fisiología , Estimulación Acústica , Adulto , Señales (Psicología) , Discriminación en Psicología/fisiología , Electroencefalografía , Potenciales Evocados , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Adulto Joven
15.
Int J Psychophysiol ; 92(3): 93-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24657900

RESUMEN

Infrequent, salient stimuli often capture attention despite their task-irrelevancy, and disrupt on-going goal-directed behavior. A number of studies show that presenting cues signaling forthcoming deviants reduces distraction, which may be a "by-product" of cue-processing interference or the result of direct preparatory processes for the forthcoming distracter. In the present study, instead of "bursts" of cue information, information on the temporal structure of the stimulus sequence was provided. Young adults performed a spatial discrimination task where complex tones moving left or right were presented. In the predictable condition, every 7th tone was a pitch-deviant, while in the random condition the position of deviants was random with a probability of 1/7. Whereas the early event-related potential correlates of deviance-processing (N1 and MMN) were unaffected by predictability, P3a amplitude was significantly reduced in the predictable condition, indicating that prevention of distraction was based on the knowledge about the temporal structure of the stimulus sequence.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/prevención & control , Discriminación en Psicología/fisiología , Potenciales Evocados Auditivos/fisiología , Retroalimentación Psicológica/fisiología , Estimulación Acústica , Adulto , Análisis de Varianza , Mapeo Encefálico , Señales (Psicología) , Electroencefalografía , Femenino , Humanos , Masculino , Tiempo de Reacción , Adulto Joven
16.
Psychiatr Hung ; 28(4): 370-92, 2013.
Artículo en Húngaro | MEDLINE | ID: mdl-24443573

RESUMEN

Mild cognitive impairment (MCI) can be considered as an intermediate stage between normal cognitive aging and dementia. Its screening is extremely important because within a year in 15-20% of cases dementia can evolve. In Hungary, the most widely used screening tool for both dementia and MCI is the Mini Mental State Examination (MMSE), which is often criticized for its poor screening sensitivity of mild dementia and MCI. To eliminate this problem, the Montreal Cognitive Assessment (MoCA) was developed, especially for screening MCI. Our study presents the first results with the Hungarian translation of MoCA. We used Beck Depression Inventory (BDI) for controlling depression. In MoCA the cutoff score between healthy and MCI persons was 24 out of 30. MoCA was more sensitive in detecting MCI than MMSE and its inner consistency was also slightly higher. Specificity of the tests to detect MCI was similar. The results on BDI were not related to either MoCA or MMSE. Our results suggest that MoCA can be a useful tool to detect cognitive decline.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Demencia Vascular/diagnóstico , Demencia Vascular/psicología , Escalas de Valoración Psiquiátrica , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/epidemiología , Depresión/complicaciones , Depresión/epidemiología , Escolaridad , Femenino , Humanos , Hungría/epidemiología , Lenguaje , Masculino , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Escalas de Valoración Psiquiátrica/normas , Psicometría , Sensibilidad y Especificidad
17.
Dev Neurobiol ; 72(6): 766-76, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21954122

RESUMEN

Neurotrophins can influence multiple cellular functions depending on the cellular context and the specific receptors they interact with. These neurotrophic factors have been extensively studied for their ability to support neuronal survival via Trk receptors and to induce apoptosis via the p75(NTR). However, the p75(NTR) is also detected on cell populations that do not undergo apoptosis in response to neurotrophins. In particular, the authors have detected p75(NTR) expression on astrocytes during development and after seizure-induced injury. In this study, the authors investigated the role of Nerve growth factor (NGF) in regulating astrocyte proliferation and in influencing specific aspects of the cell cycle. The authors have demonstrated that NGF prevents the induction of cyclins and their association with specific cyclin-dependent kinases, and thereby prevents progression through the G1 phase of the cell cycle. Since the authors have previously shown that p75(NTR) but not TrkA, is expressed in astrocytes, these data suggest that activation of p75(NTR) promotes withdrawal of astrocytes from the cell cycle, which may have important consequences during development and after injury.


Asunto(s)
Astrocitos/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Factor de Crecimiento Nervioso/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Astrocitos/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/fisiología , Puntos de Control del Ciclo Celular/fisiología , Células Cultivadas , Quinasas Ciclina-Dependientes/metabolismo , Factor de Crecimiento Epidérmico/farmacología , Ratas , Ratas Sprague-Dawley , Receptor de Factor de Crecimiento Nervioso/metabolismo
18.
J Neurosci ; 30(46): 15608-15, 2010 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-21084616

RESUMEN

Proneurotrophins and mature neurotrophins activate different signaling pathways with distinct effects on their target cells: proneurotrophins can induce apoptotic signaling via p75(NTR), whereas mature neurotrophins activate Trk receptors to influence survival and differentiation. Here, we demonstrate that the PTEN (phosphatase and tensin homolog deleted on chromosome 10) phosphatase represents a novel switch between the survival and apoptotic signaling pathways in rat CNS neurons. Simultaneous activation of p75(NTR) by proNGF and TrkB signaling by BDNF elicited apoptosis despite TrkB phosphorylation. Apoptosis induced by p75(NTR) required suppression of TrkB-induced phosphoinositide-3 kinase signaling, mediated by induction of PTEN, for apoptosis to proceed. Inhibition of PTEN restored the ability of BDNF to phosphorylate Akt and protect cultured basal forebrain neurons from proNGF-induced death. In vivo, inhibition or knockdown of PTEN after pilocarpine-induced seizures protected CNS neurons from p75(NTR)-mediated death, demonstrating that PTEN is a crucial factor mediating the balance between p75(NTR)-induced apoptotic signaling and Trk-mediated survival signaling in brain neurons.


Asunto(s)
Encéfalo/fisiología , Factores de Crecimiento Nervioso/fisiología , Fosfohidrolasa PTEN/biosíntesis , Precursores de Proteínas/fisiología , Receptor trkB/antagonistas & inhibidores , Receptor trkB/fisiología , Receptores de Factor de Crecimiento Nervioso/fisiología , Transducción de Señal/fisiología , Animales , Encéfalo/citología , Encéfalo/metabolismo , Muerte Celular/fisiología , Supervivencia Celular/fisiología , Células Cultivadas , Femenino , Masculino , Proteínas del Tejido Nervioso , Neuronas/metabolismo , Neuronas/fisiología , Fosfohidrolasa PTEN/antagonistas & inhibidores , Fosfohidrolasa PTEN/genética , Embarazo , Ratas , Ratas Sprague-Dawley , Receptores de Factores de Crecimiento
19.
J Neurosci ; 28(39): 9870-9, 2008 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-18815271

RESUMEN

Seizure-induced damage elicits a loss of hippocampal neurons mediated to a great extent by the p75 neurotrophin receptor (NTR). Proneurotrophins, which are potent apoptosis-inducing ligands for p75(NTR), were increased in the hippocampus, particularly in astrocytes, by pilocarpine-induced seizures; and infusion of anti-pro-NGF dramatically attenuated neuronal loss after seizures. The p75(NTR) is expressed in many different cell types in the nervous system, and can mediate a variety of different cellular functions by recruiting specific intracellular binding proteins to activate distinct signaling pathways. In this study, we demonstrate that neurotrophin receptor-interacting factor (NRIF) mediates apoptotic signaling via p75(NTR) in hippocampal neurons in vitro and in vivo. After seizure-induced injury, NRIF(-/-) mice showed an increase in p75(NTR) expression in the hippocampus; however, these neurons failed to undergo apoptosis in contrast to wild-type mice. Treatment of cultured hippocampal neurons with proneurotrophins induced association of NRIF with p75(NTR) and subsequent translocation of NRIF to the nucleus, which was dependent on cleavage of the receptor. Neurons lacking NRIF were resistant to p75(NTR)-mediated apoptosis in vitro and in vivo. In addition, we demonstrate some mechanistic differences in p75(NTR) signaling in hippocampal neurons compared with other cell types. Overall, these studies demonstrate the requirement for NRIF to signal p75(NTR)-mediated apoptosis of hippocampal neurons and that blocking pro-NGF can inhibit neuronal loss after seizures.


Asunto(s)
Apoptosis/fisiología , Hipocampo/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Factor de Crecimiento Nervioso/líquido cefalorraquídeo , Factores de Crecimiento Nervioso/metabolismo , Neuronas/metabolismo , Precursores de Proteínas/líquido cefalorraquídeo , Receptor de Factor de Crecimiento Nervioso/metabolismo , Convulsiones/patología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Proteínas de Unión al ADN , Modelos Animales de Enfermedad , Ensayo de Cambio de Movilidad Electroforética/métodos , Embrión de Mamíferos , Femenino , Fluoresceínas , Péptidos y Proteínas de Señalización Intracelular/deficiencia , Masculino , Ratones , Ratones Noqueados , Neuronas/efectos de los fármacos , Compuestos Orgánicos/metabolismo , Pilocarpina , Embarazo , Ratas , Convulsiones/inducido químicamente , Factores de Tiempo
20.
Behav Brain Res ; 172(2): 324-32, 2006 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-16814878

RESUMEN

The current research studied the behavior adopted in the elevated plus maze (EPM) of rats previously subjected to a social defeat using the resident-intruder paradigm. One day after defeat, intruder animals exhibited an anxiogenic-like behavior in the EPM. In addition, we also evaluated the role of the corticosteroid receptor system (minerlocorticoid - MR - and glucocorticoid - GR - receptors) from the lateral septum (LS) on the anxiety generated by social defeat. The LS is an area of the aversive circuitry that is preferentially activated in passive defensive postures, and participates - together with other brain areas - in the modulation of aversive states. Intruder animals were infused into the LS with the MR or GR antagonist (ZK 91587 and RU 38486, respectively) and then submitted to social stress. All rats were tested in the EPM 1 day later. Only the administration of the GR antagonist, but not the MR antagonist, into the LS normalized the anxiogenic response induced by defeat. Furthermore, we examined whether a single injection of corticosterone (CS) could induce the same influence on the behavior in the EPM as that observed after social defeat. Moreover, we explored the effect of local infusions of MR or GR antagonists into the LS on the behavior exhibited by CS-treated rats in a subsequent EPM exposure. CS administration also exerted an increased anxiogenic-like behavior, which was normalized only by the local infusion of the GR antagonist. Based on these findings, we suggest that CS secreted by emotionally relevant stimuli acting via GR in LS plays an important role in the modulation of the emotional sequelae induced by social defeat.


Asunto(s)
Ansiedad/metabolismo , Corticosterona/fisiología , Dominación-Subordinación , Receptores de Glucocorticoides/metabolismo , Núcleos Septales/metabolismo , Análisis de Varianza , Animales , Reacción de Prevención/fisiología , Emociones/fisiología , Conducta Exploratoria/fisiología , Femenino , Masculino , Ratas , Ratas Wistar , Receptores de Mineralocorticoides/metabolismo , Medio Social
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