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1.
Adv Exp Med Biol ; 1191: 3-20, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32002919

RESUMEN

Magnetic resonance imaging (MRI) is a good tool for researchers to understand the biological mechanisms and pathophysiology of the brain due to the translational characteristics of MRI methods. For the psychiatric illness, this kind of mental disorders usually have minor alterations when compared to traditional neurological disorders. Therefore the functional study, such as functional connectivity, would play a significant role for understanding the pathophysiology of mental disorders. This chapter would focus on the discussion of task MRI-based functional network studies in anxiety. For social anxiety disorder, the limbic system, such as the temporal lobe, amygdala, and hippocampus, would show alterations in the functional connectivity with frontal regions, such as anterior cingulate, prefrontal, and orbitofrontal cortices. PD has anterior cingulate cortex-amygdala alterations in fear conditioning, frontoparietal alterations in attention network task, and limbic-prefrontal alterations in emotional task. A similar amygdala-based aberrant functional connectivity in specific phobia is observed. The mesocorticolimbic and limbic-prefrontal functional alterations are found in generalized anxiety disorder. The major components of task MRI-based functional connectivity in anxiety include limbic and frontal regions which might play a vital role for the origination of anxiety under different scenarios and tasks.


Asunto(s)
Trastornos de Ansiedad/fisiopatología , Ansiedad/fisiopatología , Mapeo Encefálico , Encéfalo/fisiopatología , Imagen por Resonancia Magnética , Humanos
2.
Adv Exp Med Biol ; 1191: 21-34, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32002920

RESUMEN

Network-based approach for psychological phenotypes assumes the dynamical interactions among the psychiatric symptoms, psychological characteristics, and neurocognitive performances arise, as they coexist, propagate, and inhibit other components within the network of mental phenomena. For differential types of dataset from which the phenotype network is to be estimated, a Gaussian graphical model, an Ising model, a directed acyclic graph, or an intraindividual covariance network could be used. Accordingly, these network-based approaches for anxiety-related psychological phenomena have been helpful in quantitative and pictorial understanding of qualitative dynamics among the diverse psychological phenomena as well as mind-environment interactions. Brain structural covariance refers to the correlative patterns of diverse brain morphological features among differential brain regions comprising the brain, as calculated per participant or across the participants. These covarying patterns of brain morphology partly overlap with longitudinal patterns of brain cortical maturation and also with propagating pattern of brain morphological changes such as cortical thinning and brain volume reduction in patients diagnosed with neurologic or psychiatric disorders along the trajectory of disease progression. Previous studies that used the brain structural covariance network could show neural correlates of specific anxiety disorder such as panic disorder and also elucidate the neural underpinning of anxiety symptom severity in diverse psychiatric and neurologic disorder patients.


Asunto(s)
Trastornos de Ansiedad/patología , Trastornos de Ansiedad/fisiopatología , Ansiedad/patología , Ansiedad/fisiopatología , Encéfalo/patología , Encéfalo/fisiopatología , Fenotipo , Humanos , Vías Nerviosas
3.
Adv Exp Med Biol ; 1191: 121-140, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32002926

RESUMEN

Discovery of innovative anxiolytics is severely hampering. Existing anxiolytics are developed decades ago and are still the therapeutics of choice. Moreover, lack of new drug targets forecasts a severe jeopardy in the future treatment of the huge population of CNS-diseased patients. We simply lack the knowledge on what is wrong in brains of anxious people (normal and diseased). Translational research, based on interacting clinical and preclinical research, is extremely urgent. In this endeavor, genetic and genomic approaches are part of the spectrum of contributing factors. We focus on three druggable targets: serotonin transporter, 5-HT1A, and GABAA receptors. It is still uncertain whether and how these targets are involved in normal and diseased anxiety processes. For serotonergic anxiolytics, the slow onset of action points to indirect effects leading to plasticity changes in brain systems leading to reduced anxiety. For GABAA benzodiazepine drugs, acute anxiolytic effects are found indicating primary mechanisms directly influencing anxiety processes. Close translational collaboration between fundamental academic and discovery research will lead to badly needed breakthroughs in the search for new anxiolytics.


Asunto(s)
Ansiolíticos/uso terapéutico , Trastornos de Ansiedad/fisiopatología , Ansiedad/fisiopatología , Descubrimiento de Drogas , Neurotransmisores/metabolismo , Investigación en Medicina Traslacional , Ansiolíticos/farmacología , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/metabolismo , Humanos
4.
Adv Exp Med Biol ; 1191: 141-153, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32002927

RESUMEN

Substantial evidence from various studies suggests a preeminent role for early adverse experiences in the development of psychopathology. The most recent studies reviewed here suggest that early life stressors are associated with an increased risk for anxiety disorders in adulthood. Early life stress predisposes individuals to develop a number of psychiatric syndromes, particularly affective disorders, including anxiety disorders, and is therefore a significant health problem.This review examines the emerging literature on the relationship between stress, hypothalamic-pituitary-adrenal (HPA) axis function, and generalized anxiety disorder (GAD), panic disorder, and phobias and the role of early life stress as an important risk factor for HPA axis dysfunction.The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolemia and reduced inhibitory feedback. In addition to melancholic depression, a spectrum of other conditions may be associated with increased and prolonged activation of the HPA axis, including panic, GAD, phobias and anxiety. Moreover, HPA axis changes appear to be state-dependent, tending to improve upon resolution of the anxiety syndrome. Interestingly, persistent HPA hyperactivity has been associated with higher rates of relapse. These studies suggest that an evaluation of the HPA axis during treatment may help identify patients who are at a higher risk for relapse. These findings suggest that this dysfunction of the HPA axis is partially attributable to an imbalance between glucocorticoid and mineralocorticoid receptors. Evidence has consistently demonstrated that glucocorticoid receptor function is impaired in anxiety disorders. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. Early stressful life events may provoke alterations of the stress response and thus of the HPA axis that can endure during adulthood, predisposing individuals to develop psychopathology.


Asunto(s)
Experiencias Adversas de la Infancia , Trastornos de Ansiedad/etiología , Trastornos de Ansiedad/fisiopatología , Ansiedad/etiología , Ansiedad/fisiopatología , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/fisiopatología , Estrés Psicológico/complicaciones , Ansiedad/psicología , Trastornos de Ansiedad/psicología , Humanos , Estrés Psicológico/psicología
5.
BJOG ; 127(3): 364-375, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31507061

RESUMEN

OBJECTIVE: Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximise primary prevention for breast-and-ovarian cancer. We compare long-term outcomes of population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life. DESIGN: Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS); (ii) FH/clinical-criteria-based testing. SETTING: North London Ashkenazi-Jewish (AJ) population. POPULATION/SAMPLE: AJ women/men. METHODS: Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population. INCLUSION CRITERIA: AJ women/men >18 years old; exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers. INTERVENTIONS: Genetic testing for three Jewish BRCA founder-mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm; (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality-of-life outcomes over 3 years. MAIN OUTCOME MEASURES: Validated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality-of-life outcomes at baseline/1-year/2-year/3-year follow up. RESULTS: In all, 1034 individuals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety-&-depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health-anxiety (P < 0.0005) and quality-of-life (P = 0.004) scores in both PS and FH groups over time. Eighteen of 30 (60%) BRCA carriers identified did not fulfil clinical criteria for BRCA testing. Total BRCA prevalence was 2.9% (95% CI 1.97-4.12%), BRCA1 prevalence was 1.55% (95% CI 0.89-2.5%) and BRCA2 prevalence was 1.35% (95% CI 0.74-2.26%). CONCLUSION: Population-based AJ BRCA testing does not adversely affect long-term psychological wellbeing or quality-of-life, decreases anxiety and could identify up to 150% additional BRCA carriers. TWEETABLE ABSTRACT: Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.


Asunto(s)
Ansiedad , Detección Precóz del Cáncer , Genes BRCA1 , Genes BRCA2 , Síndrome de Cáncer de Mama y Ovario Hereditario , Calidad de Vida , Adulto , Ansiedad/fisiopatología , Ansiedad/prevención & control , Detección Precóz del Cáncer/métodos , Detección Precóz del Cáncer/psicología , Femenino , Predisposición Genética a la Enfermedad/psicología , Pruebas Genéticas/métodos , Pruebas Genéticas/estadística & datos numéricos , Síndrome de Cáncer de Mama y Ovario Hereditario/diagnóstico , Síndrome de Cáncer de Mama y Ovario Hereditario/etnología , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Síndrome de Cáncer de Mama y Ovario Hereditario/psicología , Humanos , Judíos/genética , Judíos/estadística & datos numéricos , Londres/epidemiología , Masculino , Anamnesis/estadística & datos numéricos , Incertidumbre
7.
Undersea Hyperb Med ; 46(3): 271-287, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31394598

RESUMEN

Purpose: Military service members often report both affective and vestibular complaints after mild traumatic brain injury (mTBI), but associations between symptoms and vestibular deficits can be subtle and inconsistent. Methods: From two complementary studies, one of military service members with persistent post-concussive symptoms after mTBI (NCT01611194) and the other of adult volunteers with no history of brain injury (NCT01925963), affective symptoms were compared to postural control, gait, otolith and visuospatial function. Results: The studies enrolled 71 participants with mTBI and 75 normative controls. Participants with mTBI had significantly reduced postural equilibrium on the sensory organization test (SOT), and more so in those with high anxiety or post-traumatic stress. Cervical and ocular vestibular evoked myogenic potentials (cVEMP; oVEMP) showed prolonged latencies in mTBI participants compared to controls; oVEMPs were significantly delayed in mTBI participants with high anxiety, post-traumatic stress or depression. A subset of the mTBI group had abnormal tandem gait and high anxiety. Anxiety, post-traumatic stress, and depression did not correlate with performance on the 6-Minute Walk Test, visuospatial neuropsychological measures, and the Satisfaction with Life Scale in the mTBI group. Conclusion: In this study military service members with mTBI reported affective symptoms, concurrently with vestibular-balance concerns. Worse scores on affective measures were associated with abnormal findings on measures of postural control, gait and otolith function.


Asunto(s)
Ansiedad/fisiopatología , Conmoción Encefálica/fisiopatología , Depresión/fisiopatología , Balance Postural , Trastornos de la Sensación/fisiopatología , Trastornos por Estrés Postraumático/fisiopatología , Potenciales Vestibulares Miogénicos Evocados , Adulto , Anciano , Conmoción Encefálica/psicología , Femenino , Marcha/fisiología , Humanos , Masculino , Persona de Mediana Edad , Personal Militar , Pruebas Neuropsicológicas , Membrana Otolítica/fisiopatología , Síndrome Posconmocional/fisiopatología , Estudios Prospectivos , Calidad de Vida , Trastornos de la Sensación/psicología
8.
Biomed Res Int ; 2019: 8740674, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31380440

RESUMEN

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.


Asunto(s)
Ansiedad/terapia , Musicoterapia , Música , Trastornos Fóbicos/terapia , Animales , Ansiedad/fisiopatología , Modelos Animales de Enfermedad , Miedo/fisiología , Humanos , Memoria/fisiología , Trastornos Fóbicos/fisiopatología , Ratas , Ratas Sprague-Dawley
10.
Int J Mol Sci ; 20(15)2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31344805

RESUMEN

Autism Spectrum Disorder (ASD) is a developmental condition characterized by impaired communication and obsessive behavior that affects 1 in 59 children. ASD is expected to affect 1 in about 40 children by 2020, but there is still no distinct pathogenesis or effective treatments. Prenatal stress has been associated with higher risk of developing ASD in the offspring. Moreover, children with ASD cannot handle anxiety and respond disproportionately even to otherwise benign triggers. Stress and environmental stimuli trigger the unique immune cells, mast cells, which could then trigger microglia leading to abnormal synaptic pruning and dysfunctional neuronal connectivity. This process could alter the "fear threshold" in the amygdala and lead to an exaggerated "fight-or-flight" reaction. The combination of corticotropin-releasing hormone (CRH), secreted under stress, together with environmental stimuli could be major contributors to the pathogenesis of ASD. Recognizing these associations and preventing stimulation of mast cells and/or microglia could greatly benefit ASD patients.


Asunto(s)
Trastorno del Espectro Autista/fisiopatología , Encéfalo/fisiopatología , Mastocitos/metabolismo , Neuronas/metabolismo , Ansiedad/fisiopatología , Ansiedad/psicología , Trastorno del Espectro Autista/etiología , Trastorno del Espectro Autista/psicología , Miedo/psicología , Femenino , Humanos , Mastocitos/patología , Microglía/patología , Plasticidad Neuronal/genética , Neuronas/patología , Embarazo
11.
Braz J Cardiovasc Surg ; 34(3): 311-317, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31310470

RESUMEN

OBJECTIVE: To investigate the effects of preoperative anxiety relieving on electrophysiological changes in patients undergoing off-pump coronary artery bypass surgery. METHODS: A total of 61 patients at ASA III risk group in the age range of 18-65 years were enrolled in the present study. Patients were randomly divided into two groups. Group S (Sedation group) was administered 0.04 mg/kg lorazepam per os (PO) twice before the operation. Group C (control group) was not administered with any anxiolytic premedication. State Trait Anxiety Inventory (STAI-I) and Beck Anxiety Inventory (BAI) were used to evaluate the level of anxiety. Electrocardiography (ECG), pulse oximeter and standard monitoring were performed for each patient. QT and P dispersions in each derivation of all ECGs were calculated. RESULTS: Preoperative STAI-I scores were significantly lower in sedation group compared to the controls. Mean values of QT dispersion measured before induction, at the 1st minute of induction, 30th second of intubation and 4th minute of intubation in sedation group were significantly reduced compared to controls (P=0.024; P=0.027; P=0.001; P=0.033, respectively). The mean values of P dispersion measured before induction, at the 3rd minute of induction, 30th second of intubation and 4th minute of intubation in sedation group were significantly reduced compared to controls (P=0.001; P=0.020; P=0.023; P=0.005, respectively). CONCLUSION: Elevated anxiety levels in patients undergoing coronary bypass surgery have a negative effect through prolonged QT and P-wave dispersion times. Anxiolytic treatment before surgery may be useful to prevent ventricular and atrial arrhythmias and associated complications through decreasing the QT and P-wave dispersion duration.


Asunto(s)
Ansiolíticos/uso terapéutico , Ansiedad/tratamiento farmacológico , Ansiedad/fisiopatología , Puente de Arteria Coronaria Off-Pump/psicología , Electrocardiografía/psicología , Lorazepam/uso terapéutico , Cuidados Preoperatorios/métodos , Adolescente , Adulto , Anciano , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/psicología , Puente de Arteria Coronaria Off-Pump/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Reproducibilidad de los Resultados , Factores de Riesgo , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
13.
Biomed Res Int ; 2019: 3426092, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31281833

RESUMEN

Anxiety is one of the most frequent psychiatric disorders. Despite the fact that most studies describe an anxiolytic effect of testosterone, hyperandrogenemia in mothers is assumed to be related to an increased risk of mood disorders in their offspring. An increasing body of scientific evidence suggests that an altered expression of interneuronal markers of the hippocampus may be the cause of anxiety. The aim of this study was to examine the influence of maternal hyperandrogenemia on behavioral parameters of anxiety-like behavior, neuropeptide Y (NPY) and parvalbumin (PV) expression in the hippocampus, and the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex. Pregnant female Wistar albino rats were treated with testosterone undecanoate on the 20th day of gestation. Anxiety-like behavior in adult female offspring was evaluated by the elevated plus maze test and the open field. The number of PV and NPY immunoreactive cells in the hippocampus was determined immunohistochemically. The level of BDNF expression in the hippocampus and cerebral cortex was analyzed with the Western blot test. Prenatal hyperandrogenization increased anxiety-like behavior in female offspring and decreased expression of NPY+ and PV+ in the CA1 region of the hippocampus as compared to the control group. BDNF expression in the hippocampus and cerebral cortex of prenatally androgenized female offspring was significantly increased in comparison with the controls. Prenatal hyperandrogenization may be the cause of anxiety-like behavior in female offspring. Decrease in NPY and PV expression in the hippocampus may explain the possible mechanism of hyperandrogenization induced anxiety.


Asunto(s)
Ansiedad/etiología , Conducta Animal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Interneuronas/fisiología , Inhibición Neural/fisiología , Efectos Tardíos de la Exposición Prenatal/etiología , Virilismo/complicaciones , Animales , Ansiedad/sangre , Ansiedad/fisiopatología , Estradiol/sangre , Femenino , Hipocampo/fisiopatología , Aprendizaje por Laberinto , Neuropéptido Y/metabolismo , Parvalbúminas/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratas Wistar , Testosterona/administración & dosificación , Testosterona/sangre , Testosterona/farmacología , Virilismo/fisiopatología
14.
Eur J Pharmacol ; 858: 172512, 2019 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-31260653

RESUMEN

The present study was conducted to evaluate the influence of AMN082, the metabotropic glutamate receptor subtype 7 (mGlu7) allosteric agonist on different stages of memory processes connected with fear conditioning in the passive avoidance (PA) learning task in mice and negative emotional state (anxiety-like) induced by ethanol- and morphine-withdrawal in the elevated plus maze (EPM) test in rats. To perform the PA test, AMN082 (1.25, 2.5 and 5 mg/kg, i. p.) was injected to interfere with (or inhibit) acquisition, consolidation, and retrieval processes. The retention latency in each group was recorded using a step-through passive avoidance task 24 h after training. In turn, in ethanol- and morphine-withdrawal rats, the influence of AMN082 on anxiety-like behavior was estimated in the EPM test 24 h- (ethanol) and 72- h (morphine) after the last dose of repeated drug administrations. In all experimental groups, AMN082 at the dose of 5 mg/kg significantly decreased the step-through latency of long-term memory in the PA task. These AMN082 effects were reversed by MMPIP (10 mg/kg), the antagonist of mGlu7 receptor. AMN082 (2.5 and 5 mg/kg) also decreased ethanol- and morphine withdrawal-induced anxiety-like behavior in the EPM test, and this AMN082 (5 mg/kg) effect was counteracted by MMPIP pretreatment. Taken together, the results show that mGlu7 is involved in fear learning to the context and anxiety-like state connected with unpleasant experiences after ethanol- and morphine withdrawal in rodents. However, it appears that functional dissociation exists between these two AMN082 effects.


Asunto(s)
Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Compuestos de Bencidrilo/farmacología , Miedo/efectos de los fármacos , Miedo/fisiología , Memoria/efectos de los fármacos , Receptores de Glutamato Metabotrópico/agonistas , Regulación Alostérica/efectos de los fármacos , Animales , Ansiedad/fisiopatología , Ansiedad/psicología , Compuestos de Bencidrilo/uso terapéutico , Relación Dosis-Respuesta a Droga , Masculino , Consolidación de la Memoria/efectos de los fármacos , Ratones , Ratas , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico
15.
Biol Pharm Bull ; 42(7): 1059-1063, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31257279

RESUMEN

The central nervous system controls the activity states of the peripheral organs in response to various environmental changes. However, the physiological interactions across multiple organs remain largely unknown. Recently, we have developed an electrophysiological recording system that simultaneously captures neuronal population activity patterns in the brain, heartbeat signals, muscle contraction signals, respiratory signals, and vagus nerve action potentials in freely moving rodents. This paper summarizes several recent insights obtained from this recording system, including the observations that some but not all brain activity patterns are associated with peripheral organ activity in a behavioral test, and that functions across cortical networks can predict stress-induced changes in cardiac function in rats. The evidence suggests that adding information on peripheral physiological signals to behavioral data assists in a more accurate estimation of animals' mental states. The concept of such a research approach opens a new field of large-scale analysis of systemic physiological signals, termed "physiolomics," which is expected to unveil further physiological issues involving mind-body associations in health and disease.


Asunto(s)
Fenómenos Electrofisiológicos , Electrofisiología/métodos , Estrés Fisiológico/fisiología , Animales , Ansiedad/fisiopatología , Encéfalo/fisiología , Ratones , Ratas , Nervio Vago/fisiología
16.
Chin Med J (Engl) ; 132(14): 1689-1699, 2019 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-31268909

RESUMEN

BACKGROUND: Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain. METHODS: Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group, n = 32) or normal housing conditions (control group, n = 32). At 15 months of age, 16 mice were randomly selected from each group for a series of behavioral tests, including two depression-related tasks (the sucrose preference test and the tail suspension test). Three days following the last behavioral test, eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV)- and calretinin (CR)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons, and the expression levels of vesicular transporters of glutamate-1 (VGluT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC], hippocampus, and amygdala). RESULTS: Behaviorally, compared with the control group, adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ±â€Š1.97% vs. 43.11 ±â€Š2.85%, t(22) = 3.417, P = 0.003) and reduced latency to immobility in the tail suspension test (92.77 ±â€Š25.08 s vs. 33.14 ±â€Š5.95 s, t(25) = 2.394, P = 0.025), but did not affect anxiety-like behaviors and pre-pulse inhibition. At the neurobiologic level, adolescent stress down-regulated PV, not CR, inter-neuron density in the mPFC (F(1, 39) = 19.30, P < 0.001), and hippocampus (F(1, 42) = 5.823, P = 0.020) and altered the CR, not PV, inter-neuron density in the amygdala (F(1, 28) = 23.16, P < 0.001). The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09, all P < 0.004), which suggests stress-induced hypoexcitability in these regions. CONCLUSIONS: Chronic stress during adolescence increased depression-like behaviors in aged mice, which may be associated with the E/I imbalance in stress-sensitive brain regions.


Asunto(s)
Envejecimiento/fisiología , Depresión/metabolismo , Depresión/fisiopatología , Animales , Ansiedad/metabolismo , Ansiedad/fisiopatología , Encéfalo/metabolismo , Encéfalo/fisiopatología , Trastorno Depresivo/metabolismo , Trastorno Depresivo/fisiopatología , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Parvalbúminas/metabolismo , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Proteína 1 de Transporte Vesicular de Glutamato/metabolismo , Ácido gamma-Aminobutírico/metabolismo
17.
Vopr Pitan ; 88(3): 53-62, 2019.
Artículo en Ruso | MEDLINE | ID: mdl-31265775

RESUMEN

Numerous experimental and clinical studies have shown high efficiency of plant polyphenolic compounds in restoring age-related memory and learning disorders. In the present study a functional food ingredient (FFI) was obtained by sorption of an aqueous solution of bilberry leaves extract on buckwheat flour, which allowed to concentrate polyphenols and increase their storage stability. The aim of this study was to evaluate the impact of a developed FFI, enriched with bilberry leaves` polyphenols, on the anxiety level, locomotor activity, memory and spatial learning of db/db mice with genetical type 2 diabetes. Material and methods. The experiment was conducted using 10 heterozygote male db/db mice and 10 homozygote male db/+ mice as the comparison control group (7 weeks of age). According to body weight, blood glucose level, the results of insulin resistance test and elevated plus-maze (EPM) test, animals were randomized into three groups: control group C1 - db/+ animals, control group C2 and experimental group G3 - obese db/db mice. Buckwheat flour was included into the diet of C2 group in a dose 22.5 g/100 g; FFI was included into the diet of G3 group in a dose 2.5 g/100 g (that was equal to 59.2± 1.4 mg-eq gallic acid per 100 g of the diet). The anxiety level and general locomotor activity were evaluated in the EPM test. The evaluation of behavior, memory and spatial learning was performed using passive avoidance test (PAT). Glycated hemoglobin level was determined in blood, insulin and leptin levels were determined in blood plasma, general antioxidant activity was determined in liver cytosolic fraction. Results and discussion. The obtained data on biochemical parameters and insulin resistance tests showed the absence of normalizing effects of developed FFI. However, the inclusion of polyphenol-containing FFI into the diet led to beneficial changes in physiological parameters. Animals of G3 group, provided with FFI, were significantly less anxious compared to both control groups. During PAT testing of short-term memory, no animals in G3 group entered to the dark compartment (0%), what demonstrated increased learning ability and well-established memory of these animals in comparison with C1 (50%) and C2 groups (80%). Conclusion. The results prove the effectiveness of bilberry leaves` polyphenols, sorbed on the brown buckwheat flour, in the correction of central nervous system disorders in db/ db mice with genetically altered type 2 diabetes, what points at possible prospect of FFI inclusion in therapeutic products for patients with type 2 diabetes mellitus.


Asunto(s)
Ansiedad/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Aprendizaje por Laberinto , Memoria/efectos de los fármacos , Hojas de la Planta/química , Polifenoles/farmacología , Vaccinium myrtillus/química , Animales , Ansiedad/metabolismo , Ansiedad/patología , Ansiedad/fisiopatología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Masculino , Ratones , Polifenoles/química
18.
Soc Cogn Affect Neurosci ; 14(6): 591-599, 2019 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-31184751

RESUMEN

Few studies have used matched affective paradigms to compare humans and non-human primates. In monkeys with amygdala lesions and youth with anxiety disorders, we examined cross-species pupillary responses during a saccade-based, affective attentional capture task. Given evidence of enhanced amygdala function in anxiety, we hypothesized that opposite patterns would emerge in lesioned monkeys and anxious participants. A total of 53 unmedicated youths (27 anxious, 26 healthy) and 8 adult male rhesus monkeys (Macaca mulatta) completed matched behavioral paradigms. Four monkeys received bilateral excitotoxic amygdala lesions and four served as unoperated controls. Compared to healthy youth, anxious youth exhibited increased pupillary constriction in response to emotional and non-emotional distractors (F(1,48) = 6.28, P = 0.02, η2p = 0.12). Pupillary response was associated significantly with anxiety symptoms severity (F(1,48) = 5.59, P = 0.02, η2p = 0.10). As hypothesized, lesioned monkeys exhibited the opposite pattern i.e. decreased pupillary constriction in response to distractors, compared to unoperated control monkeys (F(1,32) = 24.22, P < 0.001, η2 = 0.33). Amygdala lesioned monkeys and youth with anxiety disorders show opposite patterns of pupil constriction in the context of an affective distractor task. Such findings suggest the presence of altered amygdala circuitry functioning in anxiety. Future lesion and human neuroimaging work might examine the way in which specific amygdala sub-nuclei and downstream circuits mediate these effects.


Asunto(s)
Amígdala del Cerebelo/fisiopatología , Trastornos de Ansiedad/fisiopatología , Ansiedad/fisiopatología , Atención/fisiología , Pupila/fisiología , Adolescente , Animales , Ansiedad/diagnóstico , Trastornos de Ansiedad/diagnóstico , Niño , Emociones/fisiología , Femenino , Humanos , Macaca mulatta , Masculino , Índice de Severidad de la Enfermedad
19.
Biol Psychol ; 146: 107710, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31158425

RESUMEN

There are two established electroencephalogram (EEG) indices that putatively relate to anxiety symptoms: a) the error-related negativity (ERN), which reflects endogenous threat sensitivity, and b) resting-state EEG relative right frontal activity (rRFA), which relates to approach/withdrawal motivation. We examined these indices conjointly to better elucidate differential mechanisms underlying the common anxiety phenotype in youth with autism spectrum disorder (ASD), in relation to subjective reports of symptomatology and treatment response. EEG was recorded from 53 youth with ASD who participated in a 10-week social skills intervention (SSI). More negative ERN related to higher self-reported social anxiety symptoms at baseline, and predicted improvements in self-reported social anxiety symptoms following SSI. Although rRFA did not relate to anxiety symptoms at baseline, more rRFA predicted improvement in parent-reported anxiety domains but worsening in self-reported anxiety symptoms. This study provides evidence for unique neural mechanisms of anxiety symptoms and changes in anxiety after SSI in youth with ASD.


Asunto(s)
Ansiedad/psicología , Trastorno del Espectro Autista/psicología , Terapia Conductista/métodos , Motivación/fisiología , Habilidades Sociales , Adolescente , Ansiedad/fisiopatología , Ansiedad/terapia , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/terapia , Electroencefalografía , Potenciales Evocados/fisiología , Femenino , Humanos , Masculino , Descanso/fisiología , Autoinforme , Resultado del Tratamiento , Adulto Joven
20.
J Ethnopharmacol ; 241: 112006, 2019 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-31153863

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Montanoa tomentosa Cerv. (MT) is a native plant from Mexico used in traditional medicine as a remedy for reproductive impairments and relaxing effects. In previous studies, it has been shown that the endocrine state could modify the antianxiety-like actions of anxiolytic compounds. Although women are the primary user of MT, no studies have evaluated the potential impact of the endocrine milieu on its anti-anxiety actions. AIMS OF THE STUDY: Ascertain the antianxiety effects of M. tomentosa in rats with different hormonal conditions, and to analyze the participation of the GABAA receptor in ovariectomized rats treated with MT. MATERIALS AND METHODS: The animal model of anxiety used was the elevated plus-maze (EPM). Rats' endocrine conditions were: a) Low hormone levels (rats in diestrus I and II phases); b) High hormone levels (proestrus/estrus phases); c) No hormones (ovariectomized rats); and d) Rats under progesterone withdrawal (PW). To evaluate the participation of the GABAA receptor in the anxiolytic-like action of MT the antagonist picrotoxin was used. RESULTS: Results showed that MT induced dose-dependent anxiolytic-like actions in rats with low hormone level conditions. Also, MT reduced anxiety-like behavior in female rats under PW, in contrast to diazepam which was ineffective. MT's anxiolytic-like effect was blocked by picrotoxin, suggesting the participation of the GABAA receptor complex. However, increased anxiety-like behavior was observed in rats with a high hormone level condition and low doses of MT. CONCLUSIONS: Beneficial anxiolytic-like actions of MT are observed under low hormone conditions, particularly in the PW challenge (a condition that can be related to a premenstrual period). Furthermore, the participation of the GABAA receptor is evidenced. However, hormonal variations could induce the opposite effects, hence women should be cautious.


Asunto(s)
Ansiolíticos/uso terapéutico , Ansiedad/tratamiento farmacológico , Montanoa , Extractos Vegetales/uso terapéutico , Animales , Ansiolíticos/farmacología , Ansiedad/sangre , Ansiedad/fisiopatología , Conducta Animal/efectos de los fármacos , Ciclo Estral/efectos de los fármacos , Femenino , Locomoción/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta , Progesterona/sangre , Ratas Wistar , Receptores de GABA-A/fisiología
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