RESUMO
Noradrenaline (NA) in the thalamus has important roles in physiological, pharmacological, and pathological neuromodulation. In this work, a complete characterization of NA axons and Alpha adrenoceptors distributions is provided. NA axons, revealed by immunohistochemistry against the synthesizing enzyme and the NA transporter, are present in all thalamic nuclei. The most densely innervated ones are the midline nuclei, intralaminar nuclei (paracentral and parafascicular), and the medial sector of the mediodorsal nucleus (MDm). The ventral motor nuclei and most somatosensory relay nuclei receive a moderate NA innervation. The pulvinar complex receives a heterogeneous innervation. The lateral geniculate nucleus (GL) has the lowest NA innervation. Alpha adrenoceptors were analyzed by in vitro quantitative autoradiography. Alpha-1 receptor densities are higher than Alpha-2 densities. Overall, axonal densities and Alpha adrenoceptor densities coincide; although some mismatches were identified. The nuclei with the highest Alpha-1 values are MDm, the parvocellular part of the ventral posterior medial nucleus, medial pulvinar, and midline nuclei. The nucleus with the lowest Alpha-1 receptor density is GL. Alpha-2 receptor densities are highest in the lateral dorsal, centromedian, medial and inferior pulvinar, and midline nuclei. These results suggest a role for NA in modulating thalamic involvement in consciousness, limbic, cognitive, and executive functions.
Assuntos
Norepinefrina/fisiologia , Receptores Adrenérgicos/fisiologia , Sistema Nervoso Simpático/fisiologia , Tálamo/fisiologia , Animais , Autorradiografia , Axônios/fisiologia , Dopamina beta-Hidroxilase/metabolismo , Fenômenos Eletrofisiológicos , Feminino , Macaca mulatta , Macaca nemestrina , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Receptores Adrenérgicos/efeitos dos fármacos , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/metabolismo , Sistema Nervoso Simpático/diagnóstico por imagem , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
Vagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression. While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve locus coeruleus (LC) stimulation via the nucleus of the solitary tract, which receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline levels, whereas LC lesions suppress VNS therapeutic efficacy. Noninvasive transcutaneous VNS (tVNS) uses electrical stimulation that targets the auricular branch of the vagus nerve at the cymba conchae of the ear. However, the extent to which tVNS mimics VNS remains unclear. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n = 24), using high-density EEG and pupillometry during visual fixation at rest. We compared short (3.4 s) trials of tVNS to sham electrical stimulation at the earlobe (far from the vagus nerve branch) to control for somatosensory stimulation. Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4-5 s after trial onset) that was significantly higher than following sham stimulation. We further quantified, using parallel factor analysis, how tVNS modulates idle occipital alpha (8-13Hz) activity identified in each participant. We found greater attenuation of alpha oscillations by tVNS than by sham stimulation. This demonstrates that tVNS reliably induces pupillary and EEG markers of arousal beyond the effects of somatosensory stimulation, thus supporting the hypothesis that tVNS elevates noradrenaline and other arousal-promoting neuromodulatory signaling, and mimics invasive VNS.SIGNIFICANCE STATEMENT Current noninvasive brain stimulation techniques are mostly confined to modulating cortical activity, as is typical with transcranial magnetic or transcranial direct/alternating current electrical stimulation. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to stimulate subcortical arousal-promoting nuclei, though previous studies yielded inconsistent results. Here we show that short (3.4 s) tVNS pulses in naive healthy male volunteers induced transient pupil dilation and attenuation of occipital alpha oscillations. These markers of brain arousal are in line with the established effects of invasive VNS on locus coeruleus-noradrenaline signaling, and support that tVNS mimics VNS. Therefore, tVNS can be used as a tool for studying how endogenous subcortical neuromodulatory signaling affects human cognition, including perception, attention, memory, and decision-making; and also for developing novel clinical applications.
Assuntos
Ritmo alfa/fisiologia , Reflexo Pupilar/fisiologia , Estimulação do Nervo Vago , Adulto , Nível de Alerta/fisiologia , Orelha Externa , Eletroencefalografia , Fixação Ocular , Voluntários Saudáveis , Humanos , Masculino , Norepinefrina/fisiologia , Lobo Occipital/fisiologia , Transdução de Sinais/fisiologia , Estimulação Elétrica Nervosa Transcutânea , Adulto JovemRESUMO
Acupuncture reduces pain by activating specific areas called acupoints on the patient's body. When these acupoints are fully activated, sensations of soreness, numbness, fullness, or heaviness called De qi or Te qi are felt by clinicians and patients. There are two kinds of acupuncture, manual acupuncture and electroacupuncture (EA). Compared with non-acupoints, acupoints are easily activated on the basis of their special composition of blood vessels, mast cells, and nerve fibers that mediate the acupuncture signals. In the spinal cord, EA can inhibit glial cell activation by down-regulating the chemokine CX3CL1 and increasing the anti-inflammatory cytokine interleukin-10. This inhibits P38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways, which are associated with microglial activation of the C-Jun N-terminal kinase signaling pathway and subsequent astrocyte activation. The inactivation of spinal microglia and astrocytes mediates the immediate and long-term analgesic effects of EA, respectively. A variety of pain-related substances released by glial cells such as the proinflammatory cytokines tumor necrosis factor [Formula: see text], interleukin-1[Formula: see text], interleukin-6, and prostaglandins such as prostaglandins E2 can also be reduced. The descending pain modulation system in the brain, including the anterior cingulated cortex, the periaqueductal gray, and the rostral ventromedial medulla, plays an important role in EA analgesia. Multiple transmitters and modulators, including endogenous opioids, cholecystokinin octapeptide, 5-hydroxytryptamine, glutamate, noradrenalin, dopamine, [Formula: see text]-aminobutyric acid, acetylcholine, and orexin A, are involved in acupuncture analgesia. Finally, the "Acupuncture [Formula: see text]" strategy is introduced to help clinicians achieve better analgesic effects, and a newly reported acupuncture method called acupoint catgut embedding, which injects sutures made of absorbable materials at acupoints to achieve long-term effects, is discussed.
Assuntos
Analgesia por Acupuntura , Eletroacupuntura , Neurotransmissores/fisiologia , Analgesia por Acupuntura/métodos , Pontos de Acupuntura , Hormônio Adrenocorticotrópico/fisiologia , Animais , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Quimiocina CX3CL1/metabolismo , Citocinas/metabolismo , Dopamina/fisiologia , Ácido Glutâmico/fisiologia , Hemodinâmica , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Neuroglia/fisiologia , Norepinefrina/fisiologia , Peptídeos Opioides/fisiologia , Serotonina/fisiologia , Sincalida/fisiologia , Medula Espinal/citologia , Ácido gama-Aminobutírico/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: The primary objective of this scoping review was to examine and map the range of neurophysiological impacts of human touch and eye gaze, and consider their potential relevance to the therapeutic relationship and to healing. INTRODUCTION: Clinicians, and many patients and their relatives, have no doubt as to the efficacy of a positive therapeutic relationship; however, much evidence is based on self-reporting by the patient or observation by the researcher. There has been little formal exploration into what is happening in the body to elicit efficacious reactions in patients. There is, however, a growing body of work on the neurophysiological impact of human interaction. Physical touch and face-to-face interaction are two central elements of this interaction that produce neurophysiological effects on the body. INCLUSION CRITERIA: This scoping review considered studies that included cognitively intact human subjects in any setting. This review investigated the neurophysiology of human interaction including touch and eye gaze. It considered studies that have examined, in a variety of settings, the neurophysiological impacts of touch and eye gaze. Quantitative studies were included as the aim was to examine objective measures of neurophysiological changes as a result of human touch and gaze. METHODS: An extensive search of multiple databases was undertaken to identify published research in the English language with no date restriction. Data extraction was undertaken using an extraction tool developed specifically for the scoping review objectives. RESULTS: The results of the review are presented in narrative form supported by tables and concept maps. Sixty-four studies were included and the majority were related to touch with various types of massage predominating. Only seven studies investigated gaze with three of these utilizing both touch and gaze. Interventions were delivered by a variety of providers including nurses, significant others and masseuses. The main neurophysiological measures were cortisol, oxytocin and noradrenaline. CONCLUSIONS: The aim of this review was to map the neurophysiological impact of human touch and gaze. Although our interest was in studies that might have implications for the therapeutic relationship, we accepted studies that explored phenomena outside of the context of a nurse-patient relationship. This allowed exploration of the boundary of what might be relevant in any therapeutic relationship. Indeed, only a small number of studies included in the review involved clinicians (all nurses) and patients. There was sufficient consistency in trends evident across many studies in regard to the beneficial impact of touch and eye gaze to warrant further investigation in the clinical setting. There is a balance between tightly controlled studies conducted in an artificial (laboratory) setting and/or using artificial stimuli and those of a more pragmatic nature that are contextually closer to the reality of providing nursing care. The latter should be encouraged.
Assuntos
Fixação Ocular , Massagem/tendências , Relações Enfermeiro-Paciente/ética , Tato , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Estudos de Avaliação como Assunto , Feminino , Humanos , Hidrocortisona/fisiologia , Masculino , Pessoa de Meia-Idade , Neurofisiologia , Norepinefrina/fisiologia , Ocitocina/fisiologia , Autorrelato , Resultado do Tratamento , Adulto JovemRESUMO
When a social sound category initially gains behavioral significance to an animal, plasticity events presumably enhance the ability to recognize that sound category in the future. In the context of learning natural social stimuli, neuromodulators such as norepinephrine and estrogen have been associated with experience-dependent plasticity and processing of newly salient social cues, yet continued plasticity once stimuli are familiar could disrupt the stability of sensorineural representations. Here we employed a maternal mouse model of natural sensory cortical plasticity for infant vocalizations to ask whether the engagement of the noradrenergic locus coeruleus (LC) by the playback of pup-calls is affected by either prior experience with the sounds or estrogen availability, using a well-studied cellular activity and plasticity marker, the immediate early gene c-Fos. We counted call-induced c-Fos immunoreactive (c-Fos-IR) cells in both LC and physiologically validated fields within the auditory cortex (AC) of estradiol or blank-implanted virgin female mice with either 0 or 5-days prior experience caring for vocalizing pups. Estradiol and pup experience interacted both in the induction of c-Fos-IR in the LC, as well as in behavioral measures of locomotion during playback, consistent with the neuromodulatory center's activity being an online reflection of both hormonal and experience-dependent influences on arousal. Throughout core AC, as well as in a high frequency sub-region of AC and in secondary AC, a main effect of pup experience was to reduce call-induced c-Fos-IR, irrespective of estradiol availability. This is consistent with the hypothesis that sound familiarity leads to less c-Fos-mediated plasticity, and less disrupted sensory representations of a meaningful call category. Taken together, our data support the view that any coupling between these sensory and neuromodulatory areas is situationally dependent, and their engagement depends differentially on both internal state factors like hormones and external state factors like prior experience.
Assuntos
Córtex Auditivo/fisiologia , Estradiol/fisiologia , Locus Cerúleo/fisiologia , Proteínas Proto-Oncogênicas c-fos/fisiologia , Estimulação Acústica , Animais , Córtex Auditivo/anatomia & histologia , Comportamento Animal/fisiologia , Feminino , Imuno-Histoquímica , Aprendizagem/fisiologia , Locus Cerúleo/anatomia & histologia , Camundongos , Camundongos Endogâmicos CBA , Plasticidade Neuronal/fisiologia , Norepinefrina/fisiologia , Reconhecimento Psicológico/fisiologia , Comportamento Social , Vocalização Animal/fisiologiaRESUMO
Many factors are reported to be involved in the complex pathophysiological processes of autism, suggesting that there is considerable variability in the manifestations of this disease. Several interventions are used to treat this disorder. Among them, vitamin B6 is widely used to treat the symptoms observed in autism. Vitamin B6 is beneficial for about half of autistic individuals in decreasing behavioral problems. However, until now, it remains unknown why vitamin B6 is effective for this disease. Although the exact pathogenesis is not defined, it is evident that certain neurotransmitter systems are impaired in the brains of autistic patients, causing the symptoms observed in the disease. In fact, impairment of many neurotransmitter systems has been reported, including GABA, serotonin, dopamine, and noradrenalin. Furthermore, vitamin B6 is important for the synthesis of many neurotransmitters, including GABA, serotonin, dopamine, noradrenalin, histamine, glycine, and d-serine, indicating that vitamin B6 supplementation may enhance many neurotransmitter systems. Thus, vitamin B6 supplementation can treat the impaired neurotransmitter systems in a given patient, even if the actual impaired neurotransmitter systems are not defined in that patient.
Assuntos
Transtorno Autístico/tratamento farmacológico , Vitamina B 6/uso terapêutico , Transtorno Autístico/fisiopatologia , Dopamina/fisiologia , Glicina/fisiologia , Histamina/fisiologia , Humanos , Modelos Neurológicos , Neurotransmissores/fisiologia , Norepinefrina/fisiologia , Serina/biossíntese , Serotonina/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Vitamina B 6/fisiologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
The efficiency of the memory system lies not only in its readiness to detect and retrieve old stimuli but also in its ability to detect and integrate novel information. In this review, we discuss recent evidence suggesting that the neural substrates sensitive to detecting familiarity and novelty are not entirely overlapping. Instead, these partially distinct familiarity and novelty signals are integrated to support recognition memory decisions. We propose here that the mediodorsal thalamus is critical for familiarity detection, and for combining novelty signals from the medial temporal lobe cortex with the relative familiarity outputs of computations performed in other cortical structures, especially the prefrontal cortex. Importantly, we argue that the anterior hippocampus has a prominent role in detecting novelty and in communicating this with midbrain and striatal structures. We argue that different types of novelty (absolute or contextual) engage different neurotransmitter systems that converge in the hippocampus. We suggest that contextual or unexpected novelty triggers dopaminergic hippocampal-midbrain coupling and noradrenergic-mediated pupil dilation. In contrast, absolute novelty triggers cholinergic-mediated hippocampal encoding accompanied by diminished pupil dilation. These two, distinct hippocampal encoding mechanisms both lead to later recollection but are sensitive to different types of novelty. We conclude that this neurotransmitter-mediated hippocampal encoding establishes the hippocampus in an encoding mode that briefly prevents the engagement of retrieval.
Assuntos
Acetilcolina/fisiologia , Dopamina/fisiologia , Hipocampo/fisiologia , Neocórtex/fisiologia , Rede Nervosa/fisiologia , Norepinefrina/fisiologia , Reconhecimento Psicológico/fisiologia , Tálamo/fisiologia , Acetilcolina/metabolismo , Dopamina/metabolismo , Hipocampo/metabolismo , Humanos , Neocórtex/metabolismo , Rede Nervosa/metabolismo , Norepinefrina/metabolismo , Tálamo/metabolismoRESUMO
Since a significant proportion of diabetic patients have clinical or subclinical neuropathy, there may be concerns about the use of local anaesthetics. The present study was designed to determine and compare the effects of articaine, a widely used anaesthetic in dental practice, and lidocaine on the resting and axonal stimulation-evoked release of [3H]noradrenaline ([3H]NA) in prefrontal cortex slices and the release of [3H]NA in spinal cord slices prepared from non-diabetic and streptozocin (STZ)-induced diabetic (glucose level=22.03±2.31mmol/l) rats. The peak of allodynia was achieved 9 weeks after STZ-treatment. Articaine and lidocaine inhibited the stimulation-evoked release in a concentration-dependent manner and increased the resting release by two to six times. These effects indicate an inhibitory action of these anaesthetics on Na+- and K+-channels. There was no difference in clinically important nerve conduction between non-diabetic and diabetic rats, as measured by the release of transmitter in response to axonal stimulation. The uptake and resting release of NA was significantly higher in the brain slices prepared from diabetic rats, but there were no differences in the spinal cord. For the adverse effects, the effects of articaine on K+ channels (resting release) are more pronounced compared to lidocaine. In this respect, articaine has a thiophene ring with high lipid solubility, which may present potential risks for some patients.
Assuntos
Neurônios Adrenérgicos/efeitos dos fármacos , Carticaína/farmacologia , Norepinefrina/fisiologia , Anestesia Local , Animais , Axônios/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Carticaína/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Lidocaína/metabolismo , Lidocaína/farmacologia , Masculino , Condução Nervosa/efeitos dos fármacos , Norepinefrina/metabolismo , Córtex Olfatório/citologia , Ratos , Ratos Wistar , Medula Espinal/citologia , Estreptozocina/farmacologiaRESUMO
OBJECTIVE: The norepinephrine transporter has been suggested to play a crucial role in major depressive disorder. However, norepinephrine transporter availability in major depressive disorder and its role with clinical symptoms are not known. The authors tested norepinephrine transporter availability in patients with major depressive disorder with the aim to identify any associations between test results and clinical symptoms. METHOD: The present research was a cross-sectional study in which 19 patients with major depressive disorder and 19 age- and sex-matched healthy comparison subjects underwent positron emission tomography scanning to evaluate the norepinephrine transporter availability measured by the radioligand (S,S)-[18F]FMeNER-D2. Norepinephrine transporter availability in the thalamus and its subregions was quantified in terms of nondisplaceable binding potential (BPND). The authors also analyzed the association between norepinephrine transporter availability and clinical symptoms. RESULTS: Compared with healthy subjects, patients with major depressive disorder showed 29.0% higher BPND values in the thalamus and, in particular, 28.2% higher values in the thalamic subregion anatomically connected to the prefrontal cortex. Elevated norepinephrine transporter availability in the thalamus in patients was positively correlated with attention, as measured by the Trail Making Test, part A. CONCLUSIONS: These findings revealed altered norepinephrine transmission in patients with major depressive disorder, suggesting that this alteration could be related to attention in this patient population.
Assuntos
Transtorno Depressivo Maior/fisiopatologia , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/fisiologia , Tomografia por Emissão de Pósitrons , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Adulto , Mapeamento Encefálico , Estudos Transversais , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Morfolinas , Imagem Multimodal , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Norepinefrina/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Transmissão Sináptica/fisiologiaRESUMO
BACKGROUND: Inhibitory control processes are a central executive function. Several lines of evidence suggest that the GABAergic and the norepinephrine (NE) system modulate inhibitory control processes. Yet, the effects of conjoint increases in the GABAergic and NE system activity on inhibitory control have not been examined. OBJECTIVE/HYPOTHESIS: We examine the conjoint effects of the GABA and NE system for inhibitory control. METHODS: We used transcutaneous vagus nerve stimulation (tVNS), which has been shown to modulate both the GABAergic and NE system. We examine the effects of tVNS in two experimental paradigms examining different aspect of inhibitory control; i.e. a backward inhibition paradigm and a response inhibition paradigm modulating working memory load. RESULTS: There were no effects of tVNS on backward inhibition processes, but on response inhibition processes. Yet, these only emerged when working memory processes were needed to control response inhibition. Compared to a sham stimulation, tVNS induced better response inhibition performance (i.e. fewer false alarms). CONCLUSIONS: A concomitant modulation of the GABAergic and NE system, as induced by tVNS, affects inhibitory control processes, but only when working memory processes play an important role for inhibitory control. Even though both the GABAergic and the NE system are modulated by tVNS, the results suggest that the modulation of the NE system is most important for the emerging effects.
Assuntos
Função Executiva/fisiologia , Inibição Psicológica , Norepinefrina/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Estimulação do Nervo Vago/métodos , Ácido gama-Aminobutírico/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Our previous work has shown that cerebellar interposed nucleus (IN) modulates immune function. Herein, we reveal mechanism underlying the immunomodulation. Treatment of bilateral cerebellar IN of rats with 3-mercaptopropionic acid (3-MP), a glutamic acid decarboxylase antagonist that reduces γ-aminobutyric acid (GABA) synthesis, enhanced cellular and humoral immune responses to bovine serum albumin, whereas injection of vigabatrin, a GABA-transaminase inhibitor that inhibits GABA degradation, in bilateral cerebellar IN attenuated the immune responses. The 3-MP or vigabatrin administrations in the cerebellar IN decreased or increased hypothalamic GABA content and lymphoid tissues' norepinephrine content, respectively, but did not alter adrenocortical or thyroid hormone levels in serum. In addition, a direct GABAergic projection from cerebellar IN to hypothalamus was found. These findings suggest that GABAergic neurons in cerebellar IN regulate immune system via hypothalamic and sympathetic pathways.
Assuntos
Núcleos Cerebelares/imunologia , Neurônios GABAérgicos/imunologia , Hipotálamo/imunologia , Imunidade Celular/fisiologia , Imunidade Humoral/fisiologia , Sistema Nervoso Simpático/imunologia , Corticosteroides/sangue , Animais , Bovinos , Núcleos Cerebelares/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Hipotálamo/metabolismo , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunoglobulina M/biossíntese , Imunoglobulina M/genética , Linfonodos/imunologia , Linfonodos/metabolismo , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Linfocinas/biossíntese , Linfocinas/genética , Vias Neurais/fisiologia , Norepinefrina/fisiologia , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/imunologia , Hormônios Tireóideos/sangue , Ácido gama-Aminobutírico/metabolismoRESUMO
Critical periods are developmental windows during which the stimuli an animal encounters can reshape response properties in the affected system to a profound degree. Despite this window's importance, the neural mechanisms that regulate it are not completely understood. Pioneering studies in visual cortex initially indicated that norepinephrine (NE) permits ocular dominance column plasticity during the critical period, but later research has suggested otherwise. More recent work implicating NE in experience-dependent plasticity in the adult auditory cortex led us to re-examine the role of NE in critical period plasticity. Here, we exposed dopamine ß-hydroxylase knock-out (Dbh(-/-)) mice, which lack NE completely from birth, to a biased acoustic environment during the auditory cortical critical period. This manipulation led to a redistribution of best frequencies (BFs) across auditory cortex in our control mice, consistent with prior work. By contrast, Dbh(-/-) mice failed to exhibit the expected redistribution of BFs, even though NE-deficient and NE-competent mice showed comparable auditory cortical organization when reared in a quiet colony environment. These data suggest that while intrinsic tonotopic patterning of auditory cortical circuitry occurs independently from NE, NE is required for critical period plasticity in auditory cortex.
Assuntos
Córtex Auditivo/crescimento & desenvolvimento , Córtex Auditivo/fisiologia , Aprendizagem/fisiologia , Plasticidade Neuronal/fisiologia , Norepinefrina/fisiologia , Estimulação Acústica , Animais , Limiar Auditivo/fisiologia , Mapeamento Encefálico , Período Crítico Psicológico , Dopamina beta-Hidroxilase/genética , Dopamina beta-Hidroxilase/metabolismo , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Percepção da Altura Sonora/fisiologiaRESUMO
Ferulic acid is a polyphenol that has antioxidant, anti-inflammatory and anticancer properties. The present study analyzed the antidepressant-like potential of ferulic acid using two well-validated mouse models of despair test, tail suspension and forced swim tests. The results suggested that ferulic acid treatment at doses of 10, 20, 40 and 80 mg/kg (p.o.) significantly reduced the immobility time in both of these two tests. These doses that affected the depressive-like behaviors did now show any effect on locomotion counts. The further neurochemical assays suggested that ferulic acid increased monoamine neurotransmitter levels in the brain regions that are relative to mood disorders: the hippocampus and frontal cortex. The increased tend to serotonin and norepinephrine was also found in the hypothalamus after higher dose of ferulic acid treatment. The subsequent study suggested that monoamine oxidase A (MAO-A) activity was inhibited in the frontal cortex and hippocampus when treatment with 40 and 80 mg/kg ferulic acid; while MAO-B activity did not change significantly. The current study provides the first lines of evidence that serotonin and norepinephrine, but not dopamine levels were elevated in mouse hippocampus and frontal cortex after ferulic acid treatment. These changes may be attributable to the inhibition of MAO-A activities in the same brain regions.
Assuntos
Antidepressivos/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Norepinefrina/fisiologia , Serotonina/fisiologia , Animais , Antidepressivos/farmacologia , Corpo Estriado/química , Corpo Estriado/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Lobo Frontal/química , Lobo Frontal/efeitos dos fármacos , Hipocampo/química , Hipocampo/efeitos dos fármacos , Hipotálamo/química , Hipotálamo/efeitos dos fármacos , Imipramina/farmacologia , Imipramina/uso terapêutico , Imobilização , Masculino , Camundongos , Camundongos Endogâmicos ICR , Moclobemida/farmacologia , Moclobemida/uso terapêutico , Monoaminoxidase/análise , Inibidores da Monoaminoxidase/farmacologia , Atividade Motora/efeitos dos fármacos , Norepinefrina/análise , Esforço Físico/efeitos dos fármacos , Serotonina/análise , Estresse Fisiológico , Estresse Psicológico , NataçãoRESUMO
BACKGROUND: Activated hexose correlated compound (AHCC), derived from shiitake mushrooms, increases resistance to infection in immunocompromised hosts with positive effects on dendritic cells, natural killer cell function and interleukin 12 production. It may also be attenuating the systemic inflammatory response by regulating the secretion of cortisol and norepinephrine (NE). METHODS: Female Swiss-Weber mice were pretreated with AHCC (Amino Up Chemical Co., Sapporo, Japan) or water by gavage for 10 days before undergoing cecal ligation and puncture (CLP). Peritoneal exudate cells and blood samples were harvested at 4 hours and 24 hours following CLP. Plasma and peritoneal concentrations of cortisol and NE were obtained using enzyme-linked immunosorbent assay. Peritoneal bacteria were quantified by colony counts after 4 hours and 24 hours. Significance was denoted by a p < 0.05. RESULTS: Plasma and peritoneal cortisol concentrations were increased 4 hours after CLP compared with normal controls, with no difference between the pretreated groups. Concentrations of cortisol decreased from 4 hours to 24 hours after CLP with AHCC (plasma, p = 0.009; peritoneal, p < 0.001), and peritoneal cortisol at 24 hours was lower with AHCC as compared with water (p = 0.028). There was no change in plasma or peritoneal NE concentrations at 4 hours. At 24 hours, higher concentrations of NE were detected in both plasma and peritoneal fluid, with lower plasma concentrations in those gavaged with AHCC (p = 0.015). There was no significant difference in peritoneal bacteria counts. CONCLUSION: Enhanced immune function observed with AHCC could be caused by attenuated concentrations of stress hormones and catecholamines.
Assuntos
Hidrocortisona/fisiologia , Norepinefrina/fisiologia , Peritonite/tratamento farmacológico , Polissacarídeos/uso terapêutico , Animais , Carga Bacteriana/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Hidrocortisona/análise , Hidrocortisona/sangue , Camundongos , Norepinefrina/análise , Norepinefrina/sangue , Peritônio/química , Peritônio/microbiologia , Peritonite/sangue , Peritonite/fisiopatologiaRESUMO
PURPOSE: Prolonged exhaustive exercise induces a failure of the nervous system to activate the involved muscles maximally (i.e., central fatigue). Part of central fatigue may reflect insufficient output from the motor cortex (i.e., supraspinal fatigue), but the cause is unresolved. To investigate the potential link between supraspinal fatigue and changes in brain concentration of dopamine and noradrenaline in temperate environment, we combined neurophysiological methods and pharmacological manipulation of these two neurotransmitters. METHODS: Changes in performance of a cycling exercise (time trial [TT]) were tested after oral administration of placebo (Pla), dopamine, or noradrenaline reuptake inhibitors (methylphenidate and reboxetine [Rebox], respectively) in well-trained male subjects. Changes in voluntary activation, corticospinal excitability, and muscle contractile properties were tested in the knee extensors using transcranial magnetic stimulation and motor nerve electrical stimulation before and after exercise. A psychomotor vigilance task (PVT) was also performed. RESULTS: Compared with Pla, methylphenidate did not affect exercise performance (P = 0.19), but more time was needed to complete the TT after administration of Rebox (approximately 9%, P < 0.05). For the latter condition, the reduced performance was accompanied by a central/supraspinal fatigue (5%-6%, P < 0.05) and worsened PVT performance (7%, P < 0.05). For the three conditions, corticospinal excitability was unchanged, and peripheral fatigue was similar. Because the ingestion of Rebox induced a greater decrease in voluntary activation and PVT performance after the TT than Pla, with no modification in corticospinal excitability, the noradrenaline reuptake inhibitor likely affected supraspinal circuits located before the motor cortex. CONCLUSION: These results suggest that noradrenaline, but not dopamine reuptake inhibition, contributes to the development of central/supraspinal fatigue after a prolonged cycling exercise performed in temperate conditions.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Metilfenidato/farmacologia , Morfolinas/farmacologia , Córtex Motor/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Fadiga Muscular/efeitos dos fármacos , Adulto , Desempenho Atlético/fisiologia , Ciclismo , Dopamina/fisiologia , Humanos , Masculino , Córtex Motor/metabolismo , Contração Muscular/fisiologia , Fadiga Muscular/fisiologia , Neurorretroalimentação , Norepinefrina/fisiologia , Aptidão Física , Tratos Piramidais , Reboxetina , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
Changes in the nutritional profile of patients with Parkinson's disease have been reported before and after deep brain stimulation surgery. The major determinants of the weight variation in Parkinson's disease are not yet understood, and the mechanism seems complex. Based on the influence of the sympathetic nervous system in metabolic syndrome obesity, the intent of the present review is to consider the role of noradrenergic modulation on weight variations in Parkinson's disease. In this review the authors raise the following hypothesis: weight variation in Parkinson's disease before and after deep brain stimulation of the subthalamic nucleus could be influenced by noradrenergic interaction between the locus coeruleus, subthalamic nucleus, and hypothalamic nucleus.
Assuntos
Norepinefrina/fisiologia , Doença de Parkinson/cirurgia , Sistema Nervoso Simpático/fisiopatologia , Peso Corporal/fisiologia , Estimulação Encefálica Profunda , Humanos , Hipotálamo/fisiopatologia , Locus Cerúleo/fisiopatologia , Núcleo Subtalâmico/fisiopatologia , Núcleo Subtalâmico/cirurgia , Redução de PesoRESUMO
CONTEXT: Polygala paniculata Linnaeus (Polygalaceae) has shown neuroprotective effects, but there is no report about its antidepressant potential. OBJECTIVE: The antidepressant-like effect of the hydroalcoholic extract from P. paniculata and some of the possible mechanisms involved in this effect were investigated in forced swimming test (FST). MATERIALS AND METHODS: Mice received extract by oral route and were submitted to FST and open-field test. Animals were forced to swim and the total immobility time was registered (6-min period). A reduction in the immobility time is considered an antidepressant-like effect. In order to investigate the involvement of the monoaminergic systems, mice were treated with pharmacological antagonists before administration of the extract. RESULTS: The acute administration of the hydroalcoholic extract from P. paniculata produced an antidepressant-like effect, since it significantly reduced the immobility time in FST (0.01-30 mg/kg) as compared to control group, without changing locomotor activity. Pretreatment of mice with yohimbine (1 mg/kg, i.p., α2-adrenoceptor antagonist), propranolol (1 mg/kg, i.p., ß-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., dopamine D1 receptor antagonist) or sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist) prevented the antidepressant-like effect of the extract in FST (30 mg/kg). Moreover, ketanserin (5 mg/kg, i.p., preferential 5-HT(2A) receptor antagonist) enhanced the effect of the extract in FST. DISCUSSION AND CONCLUSION: The results of the present study indicate that the extract from P. paniculata has an antidepressant-like action that is likely mediated by an interaction with the serotonergic (5-HT2A receptors), noradrenergic (α2 and ß-receptor) and dopaminergic (D1 and D2 receptors) systems.
Assuntos
Antidepressivos/farmacologia , Monoaminas Biogênicas/metabolismo , Polygala/química , Antagonistas Adrenérgicos/farmacologia , Animais , Dopamina/fisiologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Resposta de Imobilidade Tônica/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Norepinefrina/fisiologia , Extratos Vegetais/antagonistas & inibidores , Extratos Vegetais/farmacologia , Serotonina/fisiologia , Antagonistas da Serotonina/farmacologia , Natação/psicologiaAssuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Clonidina/farmacologia , Prazosina/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estimulação Acústica , Animais , Clonidina/uso terapêutico , Modelos Animais de Doenças , Camundongos , Norepinefrina/fisiologia , Prazosina/uso terapêutico , Reflexo de Sobressalto/efeitos dos fármacos , Reflexo de Sobressalto/fisiologiaRESUMO
The adaptive gain theory highlights the pivotal role of the locus coeruleus-noradrenergic (LC-NE) system in regulating task engagement. In humans, however, LC-NE functional dynamics remain largely unknown. We evaluated the utility of two candidate psychophysiological markers of LC-NE activity: the P3 event-related potential and pupil diameter. Electroencephalogram and pupillometry data were collected from 24 participants who performed a 37-min auditory oddball task. As predicted by the adaptive gain theory, prestimulus pupil diameter exhibited an inverted U-shaped relationship to P3 and task performance such that largest P3 amplitudes and optimal performance occurred at the same intermediate level of pupil diameter. Large phasic pupil dilations, by contrast, were elicited during periods of poor performance and were followed by reengagement in the task and increased P3 amplitudes. These results support recent proposals that pupil diameter and the P3 are sensitive to LC-NE mode.
Assuntos
Nível de Alerta/fisiologia , Cognição/fisiologia , Potenciais Evocados P300/fisiologia , Locus Cerúleo/fisiologia , Norepinefrina/fisiologia , Estimulação Acústica , Adulto , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Masculino , Neurônios/fisiologia , Pupila/fisiologiaRESUMO
Hot flashes are a common and disturbing adverse effect of hormonal therapy for cancer. Their pathophysiology is poorly understood. At present, the leading mechanistic hypothesis rests on the assumption that abrupt hormone deprivation will result in loss of negative feedback over hypothalamic noradrenaline synthesis. In this article we critically review the different theories used to explain this phenomenon. A better understanding of the pathophysiology of hot flashes may facilitate the development of new therapeutic approaches (AU)