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1.
Yi Chuan ; 42(1): 112-125, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31956101

RESUMEN

Alcohol abuse causes tissue and organ damage, and may participate neuropsychiatric diseases. Studies have shown that DNA methylation plays an important role in gene expression and behavioral changes induced by alcohol, however the causative neurobiological mechanisms have not been clarified. In this study, 32 healthy adult male SD rats were randomly divided into a drinking water control group (n=16) and a chronic alcohol exposure group (n=16). The alcohol preference and locomotor activity of rats were evaluated by two-bottle choice test (TBCT) and open-field test (OFT). DNA methylation in the medial prefrontal cortex (mPFC) tissue was detected by the reduced representative bisulfite sequencing (RRBS) technology. The methylation differential genes closely related to alcohol abuse were screened. qRT-PCR was used to verify the mRNA expression patterns of differential genes. qRT-PCR and Western blot were used to detect the expression of DNA methyltransferases (DNMTs) and methyl CpG binding protein 2 (MeCP2). Furthermore, the effect of short-term alcohol exposure (7 days) on DNMTs and MeCP2 in the mPFC of rats was tested (n=8/group). The results indicated that the methylation level of promoter region in the mPFC of rats exposed to chronic alcohol was significantly increased. In addition, the increased methylation levels in the promoter of Ntf3 and Ppm1G were accompanied by down-regulated mRNA levels in the chronic alcohol exposure group. The decreased methylation levels in the promoter of Hap1 and DUSP1 were accompanied by up-regulated mRNA levels. Furthermore, chronic alcohol exposure increased the mRNA and protein levels of DNMT3B and MeCP2. However, short term alcohol exposure did not affect their expression. This present study provides evidence that DNA methylation is associated with the development of alcohol abuse, which may be regulated by DNMT3B and MeCP2. The target genes Ntf3, Ppm1G, Hap1, and DUSP1 related to alcohol abuse were discovered as well, providing new insights into the neurobiological mechanism of alcohol abuse and the potential pharmacological targets for the treatment of alcohol abuse.


Asunto(s)
Alcoholismo/fisiopatología , Conducta Animal , Metilación de ADN , Corteza Prefrontal/fisiopatología , Animales , ADN (Citosina-5-)-Metiltransferasas/genética , Locomoción , Masculino , Proteína 2 de Unión a Metil-CpG/genética , Regiones Promotoras Genéticas , Ratas , Ratas Sprague-Dawley
2.
Adv Exp Med Biol ; 1232: 99-104, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31893400

RESUMEN

The incidence of stress-induced psychological and somatic diseases has been increasing rapidly, and it is important to clarify the neurophysiological mechanisms of stress response in order to establish effective stress management methods. We previously reported that the prefrontal cortex (PFC) plays an important role in stress response. In the present study, we employed near-infrared spectroscopy (NIRS) and electroencephalography (EEG) to investigate the characteristics of PFC activity during mental arithmetic tasks. A two-channel NIRS device was used to measure hemoglobin (Hb) concentration changes in the bilateral PFC during a mental arithmetic task (2 min) in normal adults. Simultaneously, EEG was used to also measure bilateral PFC activity during the same task. We evaluated concentration changes of oxy-Hb induced by the task while analyzing α wave changes using power spectrum analysis. It was observed that oxy-Hb in the bilateral PFC increased significantly during the task (p < 0.05), while α wave power in the PFC decreased significantly (p < 0.01). The present results indicate that mental stress tasks caused the activation of the bilateral PFC. Simultaneous measurements of NIRS and EEG are useful for evaluating the neurophysiological mechanism of stress responses in the brain.


Asunto(s)
Electroencefalografía , Fenómenos Electromagnéticos , Oxígeno , Espectroscopía Infrarroja Corta , Estrés Psicológico , Adulto , Hemoglobinas/análisis , Humanos , Oxígeno/sangre , Oxihemoglobinas/análisis , Corteza Prefrontal/fisiopatología , Estrés Psicológico/fisiopatología
3.
Medicine (Baltimore) ; 98(50): e18357, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852140

RESUMEN

BACKGROUND: Mild cognitive impairment (MCI) is a symptom characterizing cognitive decline and a transitional state between normal aging and dementia; however, there is no definitive diagnosis and treatment for MCI. Neurofeedback (NF), which is a training mechanism that employs operant conditioning to regulate brain activity, has been increasingly investigated concerning its beneficial effects for dementia and MCI. METHODS: This study investigated cognitive improvement and hemodynamic changes in the prefrontal cortex (PFC) following NF training in patients with MCI. Five patients with MCI received NF training for enhanced beta band activity in the dorsolateral PFC-16 sessions for 8 weeks-with each session divided into 9 5-minute trials. The primary outcome measure was a cognitive assessment tool: the Korean version of the Montreal Cognitive Assessment. The secondary outcome measures were the Central Nervous System Vital Signs for neurocognitive testing, hemodynamic changes using functional near-infrared spectroscopy in the PFC during a working-memory task, and Beck Depression Inventory scores. RESULTS: After completing the training, patients' cognitive function significantly improved in domains such as composite memory, cognitive flexibility, complex attention, reaction time, and executive function. Increased electroencephalogram beta power was observed over NF training sessions (Spearman rank correlation test: r = 0.746, P = .001). The threshold value for gaining positive feedback from pre-NF baseline on beta power significantly increased (Spearman rank correlation test: r = 0.805, P = .001). Hemodynamic response in PFC changed after NF training, and individual differences were identified. Specifically, hypoactivation of the hemodynamic response by emotional distraction recovered following NF training. CONCLUSION: We suggest that patients' cognitive processing efficiency was improved by the NF training. These beneficial results suggest that NF training may have potential therapeutic applications to prevent the progression from MCI to dementia. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (KCT0003433).


Asunto(s)
Ritmo beta/fisiología , Cognición/fisiología , Disfunción Cognitiva/terapia , Neurorretroalimentación/métodos , Anciano , Disfunción Cognitiva/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Corteza Prefrontal/fisiopatología , Resultado del Tratamiento
4.
J Headache Pain ; 20(1): 104, 2019 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-31711434

RESUMEN

BACKGROUND: Functional connectivity (FC) has been used to investigate the pathophysiology of migraine. Accumulating evidence is pointing toward malfunctioning of brainstem structures, i.e., the red nucleus (RN) and substantia nigra (SN), as an important factor in migraine without aura (MwoA). We aimed to identify atypical FC between the RN and SN and other brain areas in patients with MwoA and to explore the association between RN and SN connectivity changes and performance on neuropsychological tests in these patients. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were obtained from 30 patients with MwoA and 22 age-, sex-, and years of education-matched healthy controls (HC). The FC of the brainstem structures was analyzed using a standard seed-based whole-brain correlation method. The results of the brainstem structure FC were assessed for correlations with other clinical features. RESULTS: Patients with MwoA exhibited reduced left RN-based FC with the left middle frontal gyrus, reduced right RN-based FC with the ipsilateral superior parietal lobe, and increased FC with the ipsilateral cerebellum. Additionally, patients with MwoA demonstrated significantly decreased right SN-based FC with the right postcentral gyrus, left parietal lobule, and left superior frontal gyrus. Hypo-connectivity between the right SN and right postcentral gyrus was negatively correlated with disease duration (r = - 0.506, P = 0.004). Additionally, increased connectivity of the right RN to the ipsilateral cerebellar lobes was positively correlated with the Headache Impact Test-6 scores (r = 0.437, P = 0.016). CONCLUSIONS: The present study suggested that patients with MwoA have disruption in their RN and SN resting-state networks, which are associated with specific clinical characteristics. The changes focus on the regions associated with cognitive evaluation, multisensory integration, and modulation of perception and pain, which may be associated with migraine production, feedback, and development. Taken together, these results may improve our understanding of the neuropathological mechanism of migraine.


Asunto(s)
Migraña sin Aura/diagnóstico por imagen , Núcleo Rojo/diagnóstico por imagen , Sustancia Negra/diagnóstico por imagen , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/fisiopatología , Estudios de Casos y Controles , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Migraña sin Aura/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Dolor/diagnóstico por imagen , Dolor/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Núcleo Rojo/fisiopatología , Sustancia Negra/fisiopatología
5.
J Headache Pain ; 20(1): 108, 2019 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-31747874

RESUMEN

BACKGROUND: Resting-state functional connectivity (FC) MRI has widely been used to understand migraine pathophysiology and to identify an imaging marker of the disorder. Here, we review what we have learned from FC studies. METHODS: We performed a literature search on the PubMed website for original articles reporting data obtained from conventional resting-state FC recording in migraine patients compared with healthy controls or during and outside of migraine attacks in the same patients. RESULTS: We found 219 articles and included 28 in this review after screening for inclusion and exclusion criteria. Twenty-five studies compared migraine patients with healthy controls, whereas three studies investigated migraine patients during and outside of attacks. In the studies of interictal migraine more alterations of more than 20 FC networks (including amygdala, caudate nucleus, central executive, cerebellum, cuneus, dorsal attention network, default mode, executive control, fronto-parietal, hypothalamus, insula, neostriatum, nucleus accumbens, occipital lobe, periaqueductal grey, prefrontal cortex, salience, somatosensory cortex I, thalamus and visual) were reported. We found a poor level of reproducibility and no migraine specific pattern across these studies. CONCLUSION: Based on the findings in the present review, it seems very difficult to extract knowledge of migraine pathophysiology or to identify a biomarker of migraine. There is an unmet need of guidelines for resting-state FC studies in migraine, which promote the use of homogenous terminology, public availability of protocol and the a priori hypothesis in line with for instance randomized clinical trial guidelines.


Asunto(s)
Trastornos Migrañosos/fisiopatología , Adulto , Amígdala del Cerebelo/fisiopatología , Corteza Cerebral/fisiopatología , Femenino , Humanos , Hipotálamo/fisiopatología , Imagen por Resonancia Magnética , Masculino , Corteza Prefrontal/fisiopatología , Reproducibilidad de los Resultados , Tálamo/fisiopatología
6.
Adv Exp Med Biol ; 1192: 545-564, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31705513

RESUMEN

Recently, noninvasive brain stimulation (NIBS) methodologies, including TMS and tDCS, have been considered as efficacious, safe, and innovative treatments and alternatives to conventional therapies for some psychiatric disorders. Developing evidence suggests that applying rTMS and tDCS over the cognitive control network (CCN), particularly the dorsolateral prefrontal cortex (DLPFC), may improve core symptoms in various psychiatric disorders via direct impact on the cognitive control processes involved in emotion regulation. Therefore, neuromodulation of brain regions involved in the cognitive control of emotion by NIBS approaches could contribute to a paradigm shift in psychiatry. The available evidence suggests that development of effective treatment alternatives to enhance cognition is critical for patients with psychiatric disorders. The purpose of this chapter is to review the cognition-enhancing properties of tDCS and TMS and the impact of these treatments on cognitive control processes, especially those related to emotion regulation in psychiatric disorders.


Asunto(s)
Cognición/fisiología , Terapia por Estimulación Eléctrica/métodos , Emociones/fisiología , Corteza Prefrontal/fisiopatología , Estimulación Transcraneal de Corriente Directa/métodos , Estimulación Magnética Transcraneal/métodos , Humanos
7.
Acta Neurobiol Exp (Wars) ; 79(3): 232-237, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31587015

RESUMEN

Emotional stress is considered a serious pathogenetic factor of depression. In this study an ultrasound model of emotional stress developed in our laboratory was applied. It is characterized by the use of ultrasound as the stressor agent. Animals are triggered not by any organic or physical disturbances but by the perception of adverse information. This type of stress can induce depressive-like behavioral changes in rodents, manifested by decreased sucrose preference and increased time of immobility in a forced swim test. Ultrasound stress also increased the levels of oxidative stress markers. This is important, as stress has an established association with increased oxidative processes in the central nervous system. Total glutathione and carbonyl protein content were selected as relevant brain markers, as glutathione plays a critical role in cellular defensive mechanisms during oxidative stress and the level of protein carbonyls can be a measure of global protein oxidation. We demonstrated that two weeks of chronic exposure to ultrasound was enough to cause depressive-like behavioral changes in rats. Increased levels of oxidative stress markers in the hippocampus and prefrontal cortex were also observed after two weeks of such stress. The current study has two goals: the first is to study the relationship of depression and oxidative stress; the second is an additional validation of our approach to modeling stress­induced depressive-like states in rats. The present data further support the validity of the ultrasound model by expanding information related to the influence of ultrasound stress on behavioral and physiological parameters, which are of great importance in the development of stress-induced depression. A time correlation between the onset of symptoms and a change in the level of oxidative stress markers in the brain is also demonstrated.


Asunto(s)
Conducta Animal/fisiología , Depresión/fisiopatología , Estrés Oxidativo/fisiología , Estrés Psicológico/fisiopatología , Animales , Depresión/metabolismo , Trastorno Depresivo/fisiopatología , Modelos Animales de Enfermedad , Glutatión/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , Corteza Prefrontal/fisiopatología , Ratas
9.
Nat Commun ; 10(1): 3934, 2019 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-31477694

RESUMEN

Drug addiction is a chronic relapsing disorder of compulsive drug use. Studies of the neurobehavioral factors that promote drug relapse have yet to produce an effective treatment. Here we take a different approach and examine the factors that suppress-rather than promote-relapse. Adapting Pavlovian procedures to suppress operant drug response, we determined the anti-relapse action of environmental cues that signal drug omission (unavailability) in rats. Under laboratory conditions linked to compulsive drug use and heightened relapse risk, drug omission cues suppressed three major modes of relapse-promotion (drug-predictive cues, stress, and drug exposure) for cocaine and alcohol. This relapse-suppression is, in part, driven by omission cue-reactive neurons, which constitute small subsets of glutamatergic and GABAergic cells, in the infralimbic cortex. Future studies of such neural activity-based cellular units (neuronal ensembles/memory engram cells) for relapse-suppression can be used to identify alternate targets for addiction medicine through functional characterization of anti-relapse mechanisms.


Asunto(s)
Cocaína/farmacología , Condicionamiento Operante/efectos de los fármacos , Señales (Psicología) , Neuronas/fisiología , Corteza Prefrontal/efectos de los fármacos , Alcoholismo/fisiopatología , Alcoholismo/prevención & control , Animales , Cocaína/administración & dosificación , Conducta Compulsiva/fisiopatología , Conducta Compulsiva/prevención & control , Condicionamiento Operante/fisiología , Inhibidores de Captación de Dopamina/farmacología , Masculino , Corteza Prefrontal/fisiopatología , Ratas Long-Evans , Ratas Sprague-Dawley , Ratas Transgénicas , Recurrencia , Trastornos Relacionados con Sustancias/fisiopatología , Trastornos Relacionados con Sustancias/prevención & control
10.
Depress Anxiety ; 36(8): 690-700, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31373755

RESUMEN

BACKGROUND: Clinical levels of a social anxiety disorder (SAD) often appear during childhood and rise to a peak during late adolescence. The temperament trait behavioral inhibition (BI), evident early in childhood, has been linked to increased risk for SAD. Functional and structural variations in brain regions associated with the identification of, and response to, fear may support the BI-SAD relation. Whereas relevant functional studies are emerging, the few extant structural studies have focused on adult samples with mixed findings. METHODS: A moderated-mediation model was used to examine the relations between BI, SAD symptoms, and brain-volume individual differences in a sample of children at risk for anxiety (ages 9-12; N = 130, 52 BI). RESULTS: Our findings indicate that at higher levels of BI, children with smaller anterior insula volumes showed stronger correlations between BI and SAD. In addition, larger ventrolateral prefrontal cortex (vlPFC) volumes were associated with fewer SAD symptoms. CONCLUSIONS: These findings support previous reports linking SAD levels with variations in volume and reactivity in both limbic (insula) and prefrontal (vlPFC) regions. These findings set the foundation for further examination of networks of neural structures that influence the transition from BI to SAD across development, helping further clarify mechanisms of risk and resilience.


Asunto(s)
Miedo/psicología , Lóbulo Límbico/fisiopatología , Fobia Social/fisiopatología , Corteza Prefrontal/fisiopatología , Temperamento/fisiología , Adolescente , Niño , Femenino , Humanos , Lóbulo Límbico/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Corteza Prefrontal/diagnóstico por imagen , Riesgo
11.
BMC Neurosci ; 20(1): 37, 2019 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-31366391

RESUMEN

BACKGROUND: Cardiovascular conditions contribute to brain volume loss, reduced cerebrovascular health, and increased dementia risk in aging adults. Altered hippocampal connectivity has also been observed in individuals with cardiovascular conditions, yet the functional consequences of these changes remain unclear. In the present study, we collected functional magnetic resonance imaging data during memory encoding and used a psychophysiological interaction analysis to examine whether cardiovascular burden, indexed using the Framingham risk score, was associated with encoding-related hippocampal connectivity and task performance in cognitively-intact older adults between 65 and 85 years of age. Our goal was to better understand the early functional consequences of vascular and metabolic dysfunction in those at risk for cognitive decline. RESULTS: High Framingham risk scores were associated with lower total brain volumes. In addition, those with high Framingham risk scores showed an altered relationship between left hippocampal-medial prefrontal coupling and task performance compared to those with low Framingham risk scores. Specifically, we found a significant interaction of Framingham risk and learning on connectivity between the left hippocampus and primarily left midline prefrontal regions comprising the left ventral anterior cingulate cortex and medial prefrontal cortex. Those with lower Framingham risk scores showed a pattern of weaker connectivity between left hippocampal and medial prefrontal regions associated with better task performance. Those with higher Framingham risk scores showed the opposite pattern; stronger connectivity was associated with better performance. CONCLUSIONS: Findings from the current study show that amongst older adults with cardiovascular conditions, higher Framingham risk is associated with lower brain volume and altered left hippocampal-medial prefrontal coupling during task performance compared to those with lower Framingham risk scores. This may reflect a compensatory mechanism in support of memory function and suggests that older adults with elevated cardiovascular risk are vulnerable to early Alzheimer disease-like dysfunction within the episodic memory system.


Asunto(s)
Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/psicología , Hipocampo/fisiopatología , Corteza Prefrontal/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria/fisiología , Vías Nerviosas/fisiología , Factores de Riesgo
12.
J Consult Clin Psychol ; 87(9): 772-786, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31403814

RESUMEN

OBJECTIVE: Test whether a dissonance-based transdiagnostic eating disorder treatment reduces valuation of the thin beauty ideal and high-calorie binge foods, the intervention targets, and eating pathology relative to waitlist controls. METHOD: Women with Diagnostic and Statistical Manual of Mental Disorders-5 eating disorders (N = 100) were randomized to an 8-week group-implemented Body Project Treatment (BPT) redesigned to encourage rapid symptom reduction or a waitlist control condition, completing functional MRI paradigms assessing neural response to thin models and binge foods, questionnaires, and diagnostic interviews at pretest and posttest. RESULTS: Compared to controls, BPT participants showed greater reductions in responsivity of regions involved in reward valuation (ventromedial prefrontal cortex, dorsolateral prefrontal cortex, caudate) to thin models but not binge foods, pursuit of the thin ideal (d = .72), palatability ratings of binge foods (d = .78), and greater increases in attractiveness ratings of average-weight models (d = .44), the intervention targets. BPT participants also showed significantly greater reductions in body dissatisfaction (d = .83), negative affect (d = .76), and eating disorder symptoms (d = .59), and marginally greater abstinence from binge eating and compensatory behaviors (39% vs. 21%) than controls. CONCLUSIONS: Results provide novel evidence that BPT affected the hypothesized intervention targets and reduced variables that are putatively secondary to pursuit of the thin ideal, including body dissatisfaction, negative affect, and eating disorder symptoms. Symptom reductions were smaller than in past trials, suggesting that it may be optimal to reduce valuation of the thin ideal before asking participants to reduce disordered eating behaviors that are used to pursue this ideal. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Asunto(s)
Núcleo Caudado/fisiopatología , Disonancia Cognitiva , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Corteza Prefrontal/fisiopatología , Psicoterapia de Grupo/métodos , Recompensa , Adulto , Núcleo Caudado/diagnóstico por imagen , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Corteza Prefrontal/diagnóstico por imagen , Resultado del Tratamiento , Adulto Joven
13.
Neuropsychology ; 33(6): 795-807, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31448947

RESUMEN

OBJECTIVE: Alcohol use disorder (AUD) and chronic pain are widespread conditions with extensive public health burden. This review seeks to describe neuroanatomical links and major mediating influences between AUD and chronic pain, in the service of identifying factors that predict the risk of chronic pain in precipitating or facilitating AUD. METHOD: We review the neural bases of pain and the influence of AUD on processes involved in pain perception. We propose potential mechanisms involved in the development of chronic pain in AUD, and we consider implications for pain management in recovery from AUD. RESULTS: Pain is a multidimensional and subjective experience that, in its acute form, is essential for survival, but in chronic form, pain is a disorder that negatively impacts quality of life. Neural substrates involved in initiating and maintaining chronic pain include dysfunction in descending pain pathways and reward network circuitry. AUD involves preoccupation or craving, intoxication, withdrawal, and negative affect. Neural substrates of AUD involve widespread mesocorticolimbic and cerebrocerebellar networks. Both conditions involve dysfunction of extended reward and oversight circuitry, particularly prefrontal cortex. CONCLUSIONS: The interrelationship between chronic pain and AUD resides in the intersection of etiological influences, mental experiences, and neurobiological processes. Characterization of the connection between brain and behavioral abnormalities in AUD's precipitation of chronic pain-and vice versa-allows for early detection and treatment of patients at risk for developing either or both of these conditions and for preemptive interventional approaches to reduce the risk of consequent vulnerabilities and harm. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Asunto(s)
Alcoholismo/fisiopatología , Encéfalo/fisiopatología , Dolor Crónico/fisiopatología , Alcoholismo/rehabilitación , Corteza Cerebral/fisiopatología , Dolor Crónico/terapia , Ansia , Giro del Cíngulo/fisiopatología , Humanos , Vías Nerviosas , Manejo del Dolor , Corteza Prefrontal/fisiopatología , Calidad de Vida , Recompensa
14.
Mol Med Rep ; 20(3): 2303-2315, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31322177

RESUMEN

Restraint water­immersion stress (RWIS) can induce a gastric mucosal lesions within a few hours. The medial prefrontal cortex (mPFC) is involved in the RWIS process. The present study investigated the modulatory effects and molecular mechanisms of the mPFC on gastric function under an RWIS state. Male Wistar rats were divided into four groups; namely, the control, RWIS 4 h (RWIS for 4 h only), sham­operated and bilateral­lesioned (bilateral­lesioned mPFC) groups. The gastric erosion index (EI) and gastric motility (GM) were determined, and the proteomic profiles of the mPFC were assessed by isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two­dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by western blot analysis. Compared with the RWIS 4 h group and the sham­control group, the bilateral­lesioned group exhibited a significantly lower EI (P<0.01). In the bilateral­lesioned group, RWIS led to a significant decrease in EI and GM. When comparing the control and RWIS 4 h groups, 129 dysregulated proteins were identified, of which 88 were upregulated and 41 were downregulated. Gene Ontology functional analysis demonstrated that 29 dysregulated proteins, including postsynaptic density protein 95, were directly associated with axon morphology, axon growth and synaptic plasticity. Ingenuity pathway analysis revealed that the dysregulated proteins were mainly involved in neurological disease signaling pathways, including the NF­κB and ERK signaling pathways. These data indicated that the presence of the mPFC exacerbates gastric mucosal injury in awake rats during RWIS. Although the quantitative proteomic analysis elucidated the nervous system molecular targets associated with the production of gastric mucosal lesions, such as the role of PSD95. The underlying molecular mechanisms of synaptic plasticity need to be further elucidated.


Asunto(s)
Mucosa Gástrica/fisiopatología , Corteza Prefrontal/fisiopatología , Úlcera Gástrica/etiología , Estrés Psicológico/complicaciones , Animales , Masculino , Ratas Wistar , Restricción Física , Úlcera Gástrica/fisiopatología , Estrés Psicológico/fisiopatología
15.
Sci Total Environ ; 689: 1012-1022, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31280147

RESUMEN

The etiology of depression is not known, it is thought that endocrine-disrupting chemicals (EDCs) contribute to the disease. Results of our previous research have shown that nonylphenol (NP), a well-known EDC, has neurotoxic effects, however, whether NP can induce depressive behavior by affecting synaptic plasticity has not yet been clearly elucidated. The depressive behavior induced by subchronic exposure to NP and its effect on the neuronal synaptic plasticity in rats are dynamically observed. Thirty Sprague-Dawley rats were randomly divided into 3 groups: control group (C, corn oil), NP group (NP, 4 mg/kg), and depression model group (D, corticosterone 20 mg/kg). There were 8 rats in each group. The depressive behavior of rats was tested by sucrose preference test, open-field test, and forced swimming test once a month for 3 months. The serum levels of brain-derived neurotrophic factor (BDNF) and corticosterone were detected by ELISA assay, and cellular morphological changes were observed by hematoxylin-eosin (HE) staining. The number of nerve cells, the length of dendrites, and the density of dendritic spines were observed by Golgi staining, and the synaptic cleft width, the postsynaptic density (PSD) thickness, and the synaptic interface curvature were observed by transmission electron microscope. Compared with the control group, the consumption of sucrose solution decreased in the NP group at the 2nd and 3rd month compared to the 1st month (F = 9.887, P = 0.002). The number of central square entries, the central square duration, and the total distance of movement were all decreased, and the decreasing degrees at the 3rd month were greater than those at the 1st month (F = 21.191, P < 0.001; F = 9.836, P = 0.002). The time of immobility for the NP group at the 1st month was higher than that in the control group (F = 6.912, P = 0.002). The expression of BDNF in the NP-treated group was higher than the control, while the expression of corticosterone in the NP-treated group was lower than the control. In the NP group, the cytoplasm of nerve cells contracted and appeared disordered. The neuron arrangement was disordered, and the number of cells, the length of the apex, the length of the basal dendrites, and the dendritic spine density were all lower in the NP group than those in the control group. The PSD thickness, the synaptic cleft width, and synaptic interface curvatures were all decreased in the NP group when compared to the control group. Subchronic exposure to 4 mg/kg NP led to depressive behavior in rats, and the depressive behavior and alterations in synaptic plasticity were more obvious with longer exposure time.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/sangre , Depresión/fisiopatología , Disruptores Endocrinos/toxicidad , Glucocorticoides/sangre , Plasticidad Neuronal/efectos de los fármacos , Fenoles/toxicidad , Animales , Depresión/inducido químicamente , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiopatología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
16.
Acta Neurobiol Exp (Wars) ; 79(2): 184-192, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31342954

RESUMEN

Depression is a chronic illness of unknown etiology. Trace elements, such as copper and zinc, and defense antioxidants, such as catalase, are important factors that determine the clinical course of brain diseases. Furthermore, altered glucose metabolism in hippocampus and prefrontal cortex has been associated with depression. Identifying factors that can precipitate depressive-like behavior is of particular importance as it can direct clinicians towards the etiology of the disease. In this study, 16 male Sprague-Dawley rats were randomly divided into two groups: socialized and socially isolated. After one week of acclimatization, animals were housed in isolation for 14 days. Rats in the social group were socialized together for 14 days. On day 15, the forced swim test was performed and blood sugar was analyzed. The brain was removed immediately for biochemical analysis. Socially isolated rats showed more pronounced depressive-like behavior in the forced swim test than socialized rats. Moreover, socially isolated rats demonstrated significantly lower copper and zinc concentrations, as well as a marked reduction in catalase activity, in both prefrontal cortex and hippocampus compared to socialized rats. Additionally, blood sugar levels were higher in socially isolated animals. Isolation causes reduction in copper and zinc levels and catalase activity, which may precipitate depressive-like behavior in these animals.


Asunto(s)
Catalasa/metabolismo , Cobre/sangre , Hipocampo/metabolismo , Estrés Psicológico/fisiopatología , Zinc/sangre , Animales , Antioxidantes/metabolismo , Depresión/metabolismo , Trastorno Depresivo/fisiopatología , Hipocampo/fisiopatología , Masculino , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiopatología , Ratas Sprague-Dawley , Aislamiento Social
17.
Clin EEG Neurosci ; 50(6): 375-382, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31304775

RESUMEN

In the current study, we tried to evaluate the effect of transcranial direct current stimulation (tDCS) on treatment-resistant major depression. We carried out a double-blind randomized sham-controlled trial was conducted in University Hospitals. Individuals with less than 50% decrease in the intensity of depression after 8 weeks of treatment with selective serotonin reuptake inhibitors were recruited. Thirty patients (16 women) with a mean (SD) age of 47.2 (12.0) years were randomly allocated to 2 groups. For the active group we administered 2-mA stimulation 20 minutes for each session, with 30 seconds ramp-up from 0 and 30 seconds ramp-down. For the sham group we administered 30 seconds ramp-up to 2 mA, 10 seconds stimulation, 30 seconds ramp-down, and 20 minutes no current. The anode was fixed on the center of F3, and the cathode on F4, over the dorsolateral prefrontal cortex. We assessed the Hamilton Depression Rating Scale at the baseline (mean difference = 1.0, P = .630), at the last session of tDCS, and at 1-month postintervention. There were statistically significant differences in the mean Hamilton scores after the intervention, and 1 month later in favor of active group; P < .001, and P = .003, respectively. Mixed analysis of variance showed a significant difference in the mean scores for active group P = .010 and pattern of change during the study P < .001 in favor of active intervention. We concluded that tDCS is an efficient therapy for patients with resistant major depression, and the benefits would remain at least for 1 month.


Asunto(s)
Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Resistente al Tratamiento/terapia , Estimulación Transcraneal de Corriente Directa , Adulto , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/fisiopatología , Escalas de Valoración Psiquiátrica , Inhibidores de la Captación de Serotonina/uso terapéutico , Resultado del Tratamiento
18.
Neurology ; 93(3): e215-e226, 2019 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-31227617

RESUMEN

OBJECTIVE: To identify brain regions underlying interictal generalized paroxysmal fast activity (GPFA), and their causal interactions, in children and adults with Lennox-Gastaut syndrome (LGS). METHODS: Concurrent scalp EEG-fMRI was performed in 2 separately analyzed patient groups with LGS: 10 children (mean age 8.9 years) scanned under isoflurane-remifentanil anesthesia and 15 older patients (mean age 31.7 years) scanned without anesthesia. Whole-brain event-related analysis determined GPFA-related activation in each group. Results were used as priors in a dynamic causal modeling (DCM) analysis comparing evidence for different neuronal hypotheses describing initiation and propagation of GPFA between cortex, thalamus, and brainstem. RESULTS: A total of 1,045 GPFA events were analyzed (cumulative duration 1,433 seconds). In both pediatric and older groups, activation occurred in distributed association cortical areas, as well as the thalamus and brainstem (p < 0.05, corrected for family-wise error). Activation was similar across individual patients with structural, genetic, and unknown etiologies of epilepsy, particularly in frontoparietal cortex. In both groups, DCM revealed that GPFA was most likely driven by prefrontal cortex, with propagation occurring first to the brainstem and then from brainstem to thalamus. CONCLUSIONS: We show reproducible evidence of a cortically driven process within the epileptic network of LGS. This network is present early (in children) and late (in older patients) in the course of the syndrome and across diverse etiologies of epilepsy, suggesting that LGS reflects shared "secondary network" involvement. A cortical-to-subcortical hierarchy is postulated whereby GPFA rapidly propagates from prefrontal cortex to the brainstem via extrapyramidal corticoreticular pathways, whereas the thalamus is engaged secondarily.


Asunto(s)
Encéfalo/diagnóstico por imagen , Síndrome de Lennox Gastaut/diagnóstico por imagen , Adolescente , Adulto , Factores de Edad , Encéfalo/fisiopatología , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Niño , Preescolar , Electroencefalografía , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Neuroimagen Funcional , Humanos , Síndrome de Lennox Gastaut/fisiopatología , Imagen por Resonancia Magnética , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/fisiopatología , Adulto Joven
19.
PLoS One ; 14(6): e0218327, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31216313

RESUMEN

BACKGROUND AND OBJECTIVES: The Dorsolateral prefrontal cortex (DLPFC) is implicated in cognitive and emotional responses. Yet, research that investigates the causal role of the left versus right DLPFC during the processes of emotion appraisal is lacking. In the current study, transcranial direct current stimulation (tDCS) was used to disentangle the functional lateralization of the DLPFC on emotional processing in response to the anticipation of, and subsequent confrontation with emotional stimuli in healthy volunteers. METHODS: Forty-eight subjects received both active and sham (on separate days) anodal tDCS over either the left (N = 24) or right (N = 24) DLPFC. Subjects' pupil dilation (PD, a physiological marker of cognitive resource allocation) was recorded while performing an appraisal task in which negative and positive emotion eliciting images were presented, each preceded by an informative cue indicating the valence of the upcoming stimulus. RESULTS: As compared to sham stimulation, left DLPFC anodal tDCS resulted in increased PD when confronted with negative emotional images, whereas right DLPFC anodal tDCS resulted in decreased PD when confronted with emotional images, irrespective of valence. LIMITATIONS: The interpretation of pupil dilation in response to emotional stimuli is limited. CONCLUSION: These findings suggest inverse lateralized DLPFC effects on cognitive resource allocation (as measured by pupillary responses) when confronted with emotional stimuli. The current findings may shed some light on mechanisms that explain the antidepressant effects of non-invasive brain stimulation of the left DLPFC.


Asunto(s)
Atención/fisiología , Cognición/fisiología , Emociones/fisiología , Corteza Prefrontal/efectos de la radiación , Adulto , Afecto/fisiología , Afecto/efectos de la radiación , Emociones/efectos de la radiación , Femenino , Voluntarios Sanos , Humanos , Masculino , Corteza Prefrontal/fisiopatología , Estimulación Transcraneal de Corriente Directa/métodos
20.
Neural Plast ; 2019: 8527203, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31178905

RESUMEN

Patients with multiple sclerosis (PwMS) frequently suffer from fatigue, but this debilitating symptom is not yet fully understood. We propose that self-control can be conceptually and mechanistically linked to the fatigue concept and might help explain some of the diversity on how PwMS who suffer from fatigue deal with this symptom. To test this claim, we first assessed how cortical oxygenation and measures of motor and cognitive state fatigue change during a strenuous physical task, and then we tested the predictive validity of trait fatigue and trait self-control in explaining the observed changes. A sample of N = 51 PwMS first completed a test battery to collect trait measures of fatigue and self-control. PwMS then performed an isometric hand contraction task at 10% of their maximum voluntary contraction until exhaustion while we repeatedly assessed ratings of perceived cognitive and motor exertion. In addition, we continuously measured oxygenation of the prefrontal cortex (PFC) using functional near-infrared spectroscopy. Linear mixed-effect models revealed significant increases in perceived motor and cognitive exertion, as well as increases in PFC oxygenation. Hierarchical stepwise regression analyses showed that higher trait self-control predicted a less steep increase in PFC oxygenation and perceived cognitive exertion, while trait fatigue did not predict change in any dependent variable. These results provide preliminary evidence for the suggested link between self-control and fatigue. As self-control can be enhanced with training, this finding possibly has important implications for devising nonpharmacological interventions to help patients deal with symptoms of fatigue.


Asunto(s)
Fatiga/psicología , Contracción Isométrica/fisiología , Esclerosis Múltiple/psicología , Corteza Prefrontal/fisiopatología , Autocontrol , Adulto , Cognición/fisiología , Fatiga/diagnóstico por imagen , Fatiga/fisiopatología , Femenino , Neuroimagen Funcional , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/fisiopatología , Consumo de Oxígeno/fisiología , Corteza Prefrontal/diagnóstico por imagen , Autoinforme , Espectroscopía Infrarroja Corta
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