RESUMO
The present study builds on our previous study within the framework of Wyer and Collin's comprehension-elaboration theory of humor processing. In this study, an attempt is made to segregate the neural substrates of incongruity detection and incongruity resolution during the comprehension of verbal jokes. Although a number of fMRI studies have investigated the incongruity-resolution process, the differential neurological substrates of comprehension are still not fully understood. The present study utilized an event-related fMRI design incorporating three conditions (unfunny, nonsensical and funny) to examine distinct brain regions associated with the detection and resolution of incongruities. Stimuli in the unfunny condition contained no incongruities; stimuli in the nonsensical condition contained irresolvable incongruities; and stimuli in the funny condition contained resolvable incongruities. The results showed that the detection of incongruities was associated with greater activation in the right middle temporal gyrus and right medial frontal gyrus, and the resolution of incongruities with greater activation in the left superior frontal gyrus and left inferior parietal lobule. Further analysis based on participants' rating scores provided converging results. Our findings suggest a three-stage neural circuit model of verbal humor processing: incongruity detection and incongruity resolution during humor comprehension and inducement of the feeling of amusement during humor elaboration.
Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Compreensão/fisiologia , Vias Neurais/fisiologia , Senso de Humor e Humor como Assunto , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Percepção da Fala/fisiologia , Adulto JovemRESUMO
Although empathic emotion is closely related to prosocial behavior, neuronal substrate that accounts for empathy-associated prosocial action remains poorly understood. We recorded neurons in the anterior cingulate cortex (ACC) and insular cortex (InC) in rats when they observed another rat in pain. We discovered neurons with anti-mirror properties in the ACC and InC, in addition to those with mirror properties. ACC neurons show higher coupling between activation of self-in-pain and others-in-pain, whereas the InC has a higher ratio of neurons with anti-mirror properties. During others-in-pain, ACC neurons activated more when actively nose-poking toward others and InC neurons activated more when freezing. To further illustrate prosocial function, we examined neuronal activities in the helping behavior test. Both ACC and InC neurons showed specific activation to rat rescuing which is contributed by mirror, but not anti-mirror neurons. Our work indicates the functional involvement of mirror neuron system in prosocial behaviors.
RESUMO
The comprehension-elaboration theory of humor claims that the elicitation of humor can be segregated into two stages, comprehension and elaboration. Comprehension includes detection and resolution of incongruity, and elaboration involves inducement of the experience of amusement. Previous imaging research has sought to identify the neural substrates of humor processing by comparing funny and unfunny conditions. However, such studies have not been able to segregate the comprehension and elaboration stages. The present study was designed to differentiate the respective brain areas corresponding to comprehension and elaboration with an additional condition, garden path sentences. The results suggest that the bilateral inferior frontal gyri and left superior frontal gyrus may be associated with humor comprehension, whereas the cortical region in left ventromedial prefrontal cortex and the subcortical regions in bilateral amygdalae and bilateral parahippocampal gyri may be responsible for the feeling of amusement during the elaboration process.
Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Compreensão/fisiologia , Senso de Humor e Humor como Assunto , Adulto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Idioma , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
In this study, we investigated whether stress can enhance the toxicity of oligomer Abeta(1-40) in the mouse brain. Stress was applied to the animals, consisting of a 2-day inescapable foot shock followed by 3-weekly situation reminders (SRs). We found that stress significantly affected not only the amygdala-dependent (anxiety) but also the hippocampal-dependent (spatial learning and memory) behaviors through the oxidative damage caused in these two regions. However, oligomer Abeta(1-40) treatment alone did not induce behavioral impairment. In addition, combined oligomer Abeta(1-40) and stress treatment increased the glucocorticoid receptor (GR)/mineralocorticoid receptor (MR) ratio and the expression of corticotrophin releasing factor 1 (CRF-1) receptor in the hippocampus. Changes in the components of the hypothalamic-pituitary-adrenal (HPA) axis, such as the GR/MR ratio and CRF-1 level, were observed, accompanied by increasing Abeta accumulation, oxidative stress, nuclear transcription factor (NF-kappaB) hypoactivity, and apoptotic signaling in the hippocampus, and decreasing calbindin D28K and NMDA receptor 2A/2B (NR2A/2B) in the hippocampus, along with alteration of the cholinergic neurons (ChAT) in the medium septum/diagnoid band (MS/DB), noradrenergic neurons (TH) in the locus coeruleus (LC), and serotonergic neurons (5-HT) in the Raphe nucleus. Therefore, apoptosis and synaptic dysfunction in the hippocampus severely induced the impairment of spatial learning and memory. These results suggest that stress may play an important role in the early stages of Alzheimer's disease (AD), and an antioxidant strategy might be a potential therapeutic approach for stress-mediated disorders.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Deficiências da Aprendizagem/fisiopatologia , Transtornos da Memória/fisiopatologia , Fragmentos de Peptídeos/metabolismo , Percepção Espacial/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Modelos Animais de Doenças , Eletrochoque , Hipocampo/fisiopatologia , Aprendizagem/fisiologia , Locus Cerúleo/fisiopatologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Distribuição Aleatória , Núcleos da Rafe/fisiopatologiaRESUMO
Stimulation of the amygdala is known to produce pressor, depressor, or has no effects. The present study was performed to test whether amygdala cardiovascular effects are influenced by consciousness states and by different types of anesthetics. Adult rats were set up for stimulation amygdala and measurement of blood pressure in a chronic preparation. After recovery, same sites of the amygdala were stimulated electrically for several trials with the rat under conscious or anesthetic states induced by pentobarbital, urethane, ketamine, alpha-chloralose and urethane plus alpha-chloralose, respectively. The interval between any two stimulation trials was at least 2 days. The stimulation was an 80-Hz, 0.5-ms, 100-micro A square wave pulse train lasting for 15 s. Cardiovascular responsive sites were found in the central, medial, and basolateral nuclei of the amygdala. In stimulating these responsive sites, significantly different cardiovascular effects were induced under a conscious state and an anesthetized state of the animal, yet no significant differences were found among the various anesthetic agents. We conclude, that the cardiovascular influence of the amygdala is state-dependent in the rat.
Assuntos
Tonsila do Cerebelo/fisiologia , Pressão Sanguínea/fisiologia , Fenômenos Fisiológicos Cardiovasculares , Estado de Consciência/fisiologia , Inconsciência/fisiopatologia , Anestésicos Gerais/administração & dosagem , Animais , Cloralose/administração & dosagem , Estimulação Elétrica , Injeções Intraperitoneais , Ketamina/administração & dosagem , Masculino , Modelos Animais , Pentobarbital/administração & dosagem , Ratos , Ratos Wistar , Inconsciência/induzido quimicamente , Uretana/administração & dosagemRESUMO
Using a dual-serial-arithmetic paradigm, we examined whether a capacity limitation constrains the neural activation that underlies dual-task performance. Six conditions were run in the experiment (the baseline, single-addition, single-subtraction, dual-addition, dual-subtraction, and the dual-operation condition). In the baseline condition, participants were asked to remember the initial pair of numbers and ignore subsequent stimuli. In the single-addition and single-subtraction conditions, participants had to calculate a running total over a series of stimuli. In the dual-addition and dual-subtraction conditions, they had to do two arithmetic tasks involving the same operand (e.g., + 2 and + 7, - 3 and - 5). Participants performed one addition and one subtraction task (e.g., + 2 and - 7, - 3 and + 5) in the dual-operation condition. The functional magnetic resonance imaging results showed strict left prefrontal and parietal regions in the single-addition condition and bilateral activation in the single-subtraction condition. Greater activation in the prefrontal and parietal regions was observed in both the dual-operation condition and the dual-addition condition in comparison to the single-addition condition. No greater activation was observed in either the dual-operation condition or dual-subtraction condition in comparison to the single-subtraction condition. These results suggest a constraint imposed by a limit in capacity for the neural activity subserving dual-task performance when one of the tasks places high resource demands on the executive network.
Assuntos
Mapeamento Encefálico , Matemática , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Análise de Variância , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Oxigênio/sangue , Lobo Parietal/irrigação sanguínea , Córtex Pré-Frontal/irrigação sanguínea , Tempo de Reação/fisiologiaRESUMO
Although much has been learned about the role of the amygdala in Pavlovian fear conditioning, relatively little is known about the signaling pathway involved in the acquisition of an active avoidance reaction. The aim of this study is to investigate the potentiating effects of the NO-guanylate cyclase activator YC-1 on learning and memory of shuttle avoidance test in rats. YC-1 enhanced the induction of long-term potentiation (LTP) in amygdala through NO-cGMP-PKG-ERK pathway and the increase of BDNF expression. The Western blot and PCR methods were used to examine the signaling pathways involved in fear memory. It was found that YC-1 increased the avoidance responses during learning period and the memory retention lasted longer than one week. The enhancement of learning behavior by YC-1 was antagonized by intracerebroventricular injection of NOS inhibitor l-NAME, PKG inhibitor Rp-8-Br-PET-cGMPS and MEK inhibitor PD98059, indicating that NO-cGMP-PKG and ERK pathways are involved in the learning potentiating action of YC-1. In addition, YC-1 increased the activation of ERK and Akt 30 min after Day-1 training in amygdala. YC-1 also potentiated the expression of BDNF and CREB in response to fear memory test. Taken together, these findings suggest that NO-cGMP-PKG-ERK signaling pathway is involved in the action of YC-1 in enhancing the fear memory.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Proteínas Quinases Dependentes de GMP Cíclico/fisiologia , GMP Cíclico/fisiologia , Indazóis/farmacologia , Óxido Nítrico/fisiologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Potenciação de Longa Duração/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/análise , Ratos , Ratos WistarRESUMO
The present study examined a hypothesis that the right middle frontal gyrus participates in processing orthography of Chinese characters, while the left middle frontal gyrus mediates access to phonology and semantics. Brain activation during three character tasks, which required processing orthography, phonology, or semantics of Chinese characters, respectively, was measured by functional magnetic resonance imaging. Comparable neural activity in the right middle frontal gyrus was observed in all three character tasks that always demand orthographical processing. In contrast, the left middle frontal gyrus showed greater activation in the phonological and semantic tasks than in the orthographic task. These results suggest that the right and left middle frontal gyrus have dissociable functions in achieving Chinese character recognition.
Assuntos
Mapeamento Encefálico , Lobo Frontal/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Fonética , Semântica , Adulto , Povo Asiático , Feminino , Lobo Frontal/irrigação sanguínea , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Oxigênio/sangueRESUMO
The multi-dimensional nature of pain renders difficult a holistic understanding of it. The conceptual framework of pain is said to be cognitive-evaluative, in addition to being sensory-discriminative and affective-motivational. To compare participants' brain-behavior response before and after a 6-week mindfulness-based stress reduction training course on mindfulness in relation to pain modulation, three questionnaires (the Dallas Pain Questionnaire, Short Form McGill Pain Questionnaire-SFMPQ, and Kentucky Inventory of Mindfulness) as well as resting-state functional magnetic resonance imaging were administered to participants, divided into a pain-afflicted group (N = 18) and a control group (N = 16). Our results showed that the pain-afflicted group experienced significantly less pain after the mindfulness treatment than before, as measured by the SFMPQ. In conjunction, an increased connection from the anterior insular cortex (AIC) to the dorsal anterior midcingulate cortex (daMCC) was observed in the post-training pain-afflicted group and a significant correlation was found between AIC-daMCC connectivity and SFMPQ scores. The results suggest that mindfulness training can modulate the brain network dynamics underlying the subjective experience of pain.
RESUMO
Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Intoxicação por MPTP/complicações , Doenças Neurodegenerativas/prevenção & controle , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Análise de Variância , Animais , Mapeamento Encefálico , Bromodesoxiuridina/metabolismo , Modelos Animais de Doenças , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Processamento de Imagem Assistida por Computador , Intoxicação por MPTP/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/etiologia , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Wistar , Estatística como Assunto , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Evoked neural activity (ensemble single-unit activity and evoked field potential) and functional magnetic resonance imaging (fMRI) changes of the primary somatosensory cortex in response to electrical stimulation of the hind paw were studied in rats under anesthesia. The effects of stimulation frequency (ranging from 0.3 to 10 Hz) and types of anesthetics (alpha-chloralose and sodium pentobarbital) on blood oxygen level dependent (BOLD) activation and neural activation were compared. Both ensemble single-unit activity and BOLD signal changes achieved maximal activation at 3 Hz of stimulation and responses were significantly stronger under alpha-chloralose anesthesia. The maximal activation of the integral evoked potential (sigmaEP), in contrast, was the highest at 10 Hz; and the values were similar for alpha-chloralose and pentobarbital. These analyses revealed that fMRI image changes were better correlated with ensemble single-unit activity than with sigmaEP during somatosensory stimulations.
Assuntos
Oxigênio/sangue , Córtex Somatossensorial/fisiologia , Anestesia/veterinária , Animais , Cloralose , Estimulação Elétrica , Potenciais Somatossensoriais Evocados/fisiologia , Pé , Membro Posterior , Imageamento por Ressonância Magnética , Pentobarbital , Ratos , Ratos Long-EvansRESUMO
In real life, listening to music may be associated with an eyes-closed or eyes-open state. The effect of eye state on listeners' reaction to music has attracted some attention, but its influence on brain activity has not been fully investigated. The present study aimed to evaluate the electroencephalographic (EEG) markers for the emotional valence of music in different eye states. Thirty participants listened to musical excerpts with different emotional content in the eyes-closed and eyes-open states. The results showed that participants rated the music as more pleasant or with more positive valence under an eyes-open state. In addition, we found that the alpha asymmetry indices calculated on the parietal and temporal sites reflected emotion valence in the eyes-closed and eyes-open states, respectively. The theta power in the frontal area significantly increased while listening to emotional-positive music compared to emotional-negative music under the eyes-closed condition. These effects of eye states on EEG markers are discussed in terms of brain mechanisms underlying attention and emotion.
RESUMO
Adult hippocampal neurogenesis is important for learning and memory, especially after a brain injury such as ischemia. Newborn hippocampal neurons contribute to memory performance by establishing functional synapses with target cells. This study demonstrated that the maturation of hippocampal neurons is enhanced by postischemia intermittent hypoxia (IH) intervention. The effects of IH intervention in cultured neurons were mediated by increased synaptogenesis, which was primarily regulated by brain-derived neurotrophic factor (BDNF)/PI3K/AKT. Hippocampal neo-neurons expressed BDNF and exhibited enhanced presynaptic function as indicated by increases in the pSynapsin expression, synaptophysin intensity, and postsynapse density following IH intervention after ischemia. Postischemia IH-induced hippocampal neo-neurons were affected by presynaptic activity, which reflected the dynamic plasticity of the glutamatergic receptors. These alterations were also associated with the alleviation of ischemia-induced long-term memory impairment. Our results suggest that postischemia IH intervention rescued ischemia-induced spatial learning and memory impairment by inducing hippocampal neurogenesis and functional synaptogenesis via BDNF expression.
Assuntos
Isquemia Encefálica/metabolismo , Hipocampo/citologia , Transtornos da Memória/metabolismo , Memória de Longo Prazo , Neurogênese , Neurônios/citologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipóxia Celular , Células Cultivadas , Masculino , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Sinapses/metabolismoRESUMO
While it is known that some individuals can effectively perform two tasks simultaneously, other individuals cannot. How the brain deals with performing simultaneous tasks remains unclear. In the present study, we aimed to assess which brain areas corresponded to various phenomena in task performance. Nineteen subjects were requested to sequentially perform three blocks of tasks, including two unimodal tasks and one bimodal task. The unimodal tasks measured either visual feature binding or auditory pitch comparison, while the bimodal task required performance of the two tasks simultaneously. The functional magnetic resonance imaging (fMRI) results are compatible with previous studies showing that distinct brain areas, such as the visual cortices, frontal eye field (FEF), lateral parietal lobe (BA7), and medial and inferior frontal lobe, are involved in processing of visual unimodal tasks. In addition, the temporal lobes and Brodmann area 43 (BA43) were involved in processing of auditory unimodal tasks. These results lend support to concepts of modality-specific attention. Compared to the unimodal tasks, bimodal tasks required activation of additional brain areas. Furthermore, while deactivated brain areas were related to good performance in the bimodal task, these areas were not deactivated where the subject performed well in only one of the two simultaneous tasks. These results indicate that efficient information processing does not require some brain areas to be overly active; rather, the specific brain areas need to be relatively deactivated to remain alert and perform well on two tasks simultaneously. Meanwhile, it can also offer a neural basis for biofeedback in training courses, such as courses in how to perform multiple tasks simultaneously.
Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Imageamento por Ressonância Magnética , Análise e Desempenho de Tarefas , Adulto , Feminino , Humanos , Imageamento Tridimensional , Masculino , Adulto JovemRESUMO
BACKGROUND: Chronic hyperglycemia-associated inflammation plays critical roles in disease initiation and the progression of diabetic complications, including Alzheimer's disease (AD). However, the association of chronic hyperglycemia with acute inflammation of the central nervous system in the progression of AD still needs to be elucidated. In addition, recent evidence suggests that Glucagon-like peptide-1 receptor (GLP-1R) protects against neuronal damage in the brain. Therefore, the neuroprotective effects of the GLP-1R agonist exendin-4 (EX-4) against hyperglycemia/lipopolysaccharides (LPS) damage were also evaluated in this study. METHODOLOGY/PRINCIPAL FINDINGS: Ten days after streptozotocin (STZ) or vehicle (sodium citrate) treatment in mice, EX-4 treatment (10 µg/kg/day) was applied to the mice before intrahippocampal CA1 injection of LPS or vehicle (saline) and continued for 28 days. This study examined the molecular alterations in these mice after LPS and EX4 application, respectively. The mouse cognitive function was evaluated during the last 6 days of EX-4 treatment. The results showed that the activation of NF-κB-related inflammatory responses induced cognitive dysfunction in both the hyperglycemic mice and the mice that received acute intrahippocampal LPS injection. Furthermore, acute intrahippocampal LPS injection exacerbated the impairment of spatial learning and memory through a strong decrease in monoaminergic neurons and increases in astrocytes activation and apoptosis in the hyperglycemic mice. However, EX-4 treatment protected against the cognitive dysfunction resulting from hyperglycemia or/and intrahippocampal LPS injection. CONCLUSIONS/SIGNIFICANCE: These findings reveal that both hyperglycemia and intrahippocampal LPS injection induced cognitive dysfunction via activation of NF-κB-related inflammatory responses. However, acute intrahippocampal LPS injection exacerbated the progression of cognitive dysfunction in the hyperglycemic mice via a large increase in astrocytes activation-related responses. Furthermore, EX-4 might be considered as a potential adjuvant entity to protect against neurodegenerative diseases.
Assuntos
Transtornos Cognitivos/complicações , Transtornos Cognitivos/prevenção & controle , Hipocampo , Hiperglicemia/fisiopatologia , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/farmacologia , Peptídeos/farmacologia , Peçonhas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Glicemia/metabolismo , Cognição/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Exenatida , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hipoglicemiantes/farmacologia , Injeções , Insulina/sangue , Interleucina-1beta/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia , Estreptozocina/efeitos adversos , Superóxido Dismutase/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Exercise may contribute to prevention of the cognitive decline and delay the onset of the Alzheimer's disease (AD). We evaluated the effects of continuous non-shock treadmill exercise in adult and aged male APP/PS1 double mutant transgenic mice. Adult (7-8 month-old) and aged (24 month-old) male APP/PS1 transgenic and wild-type mice were randomly assigned to either sedentary or exercise groups. The exercise program included a one-week treadmill acclimatization to adapt to the novel environment. After acclimation, mice ran on a treadmill 5 days/week until sacrificed for pathological analyses. During exercise training, no tail shock was used in the exercise paradigm; only gentle tail touching was used to induce the mice to run, to minimize the stress otherwise associated with treadmill exercise. We found that the exercise program selectively improved the spatial learning and memory associated with an increase in both cholinergic neurons in the medial septum (MS)/vertical diagonal band (VDB) and serotonergic neurons in the raphe nucleus of aged APP/PS1 transgenic mice. In adult APP/PS1 transgenic mice, the exercise paradigm increased exploratory activity and reduced anxiety with an associated increase in numbers of serotonergic neurons in the raphe nucleus. In addition, the exercise paradigm also reduced amyloid-ß peptide (Aß) levels and microglia activation, but not enough to reduce the plaque loading in the hippocampus of the APP/PS1 transgenic mice. Therefore, these findings suggest that there may exist an age-related difference in the effect of continuous non-shock treadmill exercise training on AD.
Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/reabilitação , Encéfalo/patologia , Condicionamento Físico Animal/fisiologia , Amiloide/genética , Amiloide/metabolismo , Animais , Comportamento Animal , Peso Corporal , Modelos Animais de Doenças , Aprendizagem/fisiologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Transgênicos , Presenilina-1/genética , Presenilina-1/metabolismoRESUMO
This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.
Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Gastrodia/química , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Transtorno Depressivo Maior/psicologia , Modelos Animais de Doenças , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , NataçãoRESUMO
The interaction between gene and environment is known to play a major role in the etiology of several neuropsychiatric disorders, including Alzheimer's disease (AD). The present study evaluated whether environmental manipulations such as social isolation may affect the genetic predisposition to accelerate the onset of AD-related symptoms in an adult APP/PS1 double mutant transgenic mouse model. Transgenic and wild-type male mice were housed either singly or in groups from the age of 3 months, and their behavior was compared at 7 months. Isolation had several effects on the APP/PS1 transgenic mice, including exacerbating the impairment of spatial working memory associated with increased Aß42/Aß40 ratio in the hippocampus; increased levels of MnSOD in the CA1-CA3 subregions of the hippocampus, basolateral part of the amygdala (BLA), and locus coeruleus (LC); and decreased numbers of cholinergic cells in the diagonal band of Broca (DB), noradrenergic neurons in LC, serotonergic neurons in the Raphe nucleus, and levels of NMDA 2B receptor (NR2B) in the hippocampus region. Our findings demonstrate the susceptibility of APP/PS1 transgenic adult male mice to environmental manipulation and show that social isolation has remarkable effects on the genetically determined AD-like symptoms.
Assuntos
Transtornos da Memória/etiologia , Isolamento Social , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/análise , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/fisiologia , Animais , Química Encefálica , Cruzamentos Genéticos , Predisposição Genética para Doença , Masculino , Transtornos da Memória/genética , Transtornos da Memória/fisiopatologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/análise , Neurônios/química , Neurônios/patologia , Neurotransmissores/análise , Fragmentos de Peptídeos/análise , Presenilina-1/genética , Presenilina-1/fisiologia , Processamento de Proteína Pós-Traducional , Distribuição Aleatória , Receptores de N-Metil-D-Aspartato/análise , Superóxido Dismutase/análiseRESUMO
The brain regions involved with trace fear conditioning (TFC) and delayed fear conditioning (DFC) are well-characterized, but little is known about the cellular representation subsuming these types of classical conditioning. Previous evidence has shown that activation of the amygdala is required for both TFC and DFC, while TFC also involves the hippocampus for forming conditioned response to tone. Lesions of the hippocampus did not affect tone learning in DFC, but it impaired learning in TFC. Synaptic plasticity in the hippocampus, underlying a cellular representation subsuming learning and memory, is in part modulated by extra-cellular signal-regulated kinase (ERK) signaling pathway. ERK1/2 activation is required for both TFC and DFC during memory formation, but whether this pathway is involved in memory retrieval of TFC is still unknown. In the present study, we investigated changes in ERK1/2 phosphorylation after memory retrieval in groups of mice that received TFC, DFC, tone-shock un-paired conditioning, and naïve control. Our results showed that ERK1/2 phosphorylation was elevated in the hippocampal CA1 region after retrieval of all conditioned fear responses. In particular, in the TFC group, immunohistochemistry indicated higher level of ERK1/2 phosphorylation in the hippocampal pyramidal neurons 30min after tone testing. Inhibition of the ERK1/2 signaling pathway diminished fear memory elicited by a tone in TFC. Together these results suggest that the memory retrieval process in TFC is more dependent on ERK1/2 signaling pathway than that in DFC. ERK1/2 signaling is critical for retrieval associative memory of temporally noncontiguous stimuli.
Assuntos
Estimulação Acústica/efeitos adversos , Região CA1 Hipocampal/citologia , Medo , Memória/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neurônios/enzimologia , Análise de Variância , Animais , Butadienos/farmacologia , Região CA1 Hipocampal/efeitos dos fármacos , Ativação Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Nitrilas/farmacologiaRESUMO
Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9-12 months) gained significantly more weights than the sex-specific control groups. Compared with the obese female mice, the obese males had similar energy intake but developed more weight gains. The obese male mice developed hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia, but not hypertriglyceridemia. The obese females had less hyperinsulinemia and hypercholesterolemia than the obese males, and no hyperglycemia and hypertriglyceridemia. In the contextual fear conditioning and step-down passive avoidance tasks, the obese male, but not female, mice showed poorer learning performance than their normal counterparts. These learning deficits were not due to sensorimotor impairment as verified by the open-field and hot-plate tests. Although, basal synaptic transmission characteristics (input-output transfer and paired-pulse facilitation (PPF) ratio) were not significantly different between normal and HFD groups, the magnitudes of synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)) were lower at the Schaffer collateral-CA1 synapses of the hippocampal slices isolated from the obese male, but not female, mice, as compared with their sex-specific controls. Our results suggest that male mice are more vulnerable than the females to the impacts of HFD on weight gains, metabolic alterations and deficits of learning, and hippocampal synaptic plasticity.