RESUMO
Recent studies have shown that stimulus history can be decoded via the use of broadband sensory impulses to reactivate mnemonic representations.1-4. However, memories of previous stimuli can also be used to form sensory predictions about upcoming stimuli.5,6 Predictive mechanisms allow the brain to create a probable model of the outside world, which can be updated when errors are detected between the model predictions and external inputs. 7-10 Direct recordings in the auditory cortex of awake mice established neural mechanisms for how encoding mechanisms might handle working memory and predictive processes without "overwriting" recent sensory events in instances where predictive mechanisms are triggered by oddballs within a sequence.11 However, it remains unclear whether mnemonic and predictive information can be decoded from cortical activity simultaneously during passive, implicit sequence processing, even in anesthetized models. Here, we recorded neural activity elicited by repeated stimulus sequences using electrocorticography (ECoG) in the auditory cortex of anesthetized rats, where events within the sequence (referred to henceforth as "vowels," for simplicity) were occasionally replaced with a broadband noise burst or omitted entirely. We show that both stimulus history and predicted stimuli can be decoded from neural responses to broadband impulses, at overlapping latencies but based on independent and uncorrelated data features. We also demonstrate that predictive representations are dynamically updated over the course of stimulation.
Assuntos
Córtex Auditivo , Estimulação Acústica , Animais , Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Eletrocorticografia , Memória de Curto Prazo/fisiologia , Camundongos , RatosRESUMO
OBJECTIVE: To investigate the preventive effects and possible underlying mechanism of different extracts of Kanggushu () on osteoporosis in ovariectomized rats. METHODS: One hundred and sixtyfive female SD rats were divided into 11 groups: control, sham, model, Xianling Gubao Capsule (), nilestriol, Kanggushu aqueous extract high-, medium-, and low-dose and suet extract high-, medium-, and low-dose groups. The osteoporosis model was made by ovariectomizing the rats. The latter 8 groups were administered intragastricly with Xianling Gubao Capsule, nilestriol, Kanggushu aqueous extract and suet extract for 12 weeks, respectively, while the other 3 groups were administered orally saline. The whole body bone mineral density, bone mineral content, organ coefficient of uterus, serum estradiol and alkaline phosphatase contents, blood calcium, phosphorus, interleukin 6 and bone Gla-protein levels after treatment were monitored. Additionally, three-point bending test of femur, HE staining, and scanning electron microscope were performed to explore the pharmacodynamics and underlying mechanisms. RESULTS: In comparison with ovariectomized rats of model group, Kanggushu aqueous extract high-dose resulted in an increased bone mineral density, bone mineral content and organ coefficient of uterus, improved estradiol level, and improved maximum load and structural stiffness (P<0.05 or P<0.01). Two-dimensional and three-dimensional trabecular structure was also observed under HE staining and scanning electron microscopy, and the number and thickness of trabecular bone in Kanggushu aqueous extract high-dose group was significantly increased compared to the model group, while the lipid droplets in bone marrow cavity were significantly less. However, there were no significant differences in blood calcium, total serum alkaline phosphatase and bone Gla protein among different treatment groups. Overall, the osteoprotective effects of Kanggushu aqueous extract were comparable to those of nilestriol and were significantly more effective than those of Xianling Gubao Capsule. CONCLUSION: The preventive effects of Kanggushu aqueous extract might be partly due to the increased estradiol level, accelerated restoration of bone trabecular reticulate structure, and accordingly increased bone mineral density in osteoporosis rats.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Fosfatase Alcalina/metabolismo , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Cálcio/metabolismo , Modelos Animais de Doenças , Estradiol/sangue , Feminino , Fêmur/efeitos dos fármacos , Fêmur/patologia , Fêmur/fisiopatologia , Fêmur/ultraestrutura , Interleucina-6/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Osteocalcina/metabolismo , Osteoporose/sangue , Osteoporose/fisiopatologia , Ovariectomia , Fósforo/metabolismo , Ratos , Ratos Sprague-Dawley , Útero/efeitos dos fármacos , Útero/patologiaRESUMO
In the present study, the protective effects of gypenosides from Gynostemma pentaphyllum on fatty liver disease (FLD) were examined in rats treated with high fat and cholesterol diet and alcohol. Male SD rats were divided into seven groups: control, model, lovastatin, silymarin, gypenosides high-, medium- and low-treatment groups. The latter 6 groups were fed high-fat and cholesterol diet and administered alcohol intragastricly once a day. Body weight was measured every week for 10 weeks, and the hepatic index was measured after 10 weeks. Compared with model group, levels of serum triglyceride (TG), total cholesterol (TC), free fatty acid (FFA), and low density lipoprotein cholesterol (LDL-C) level, malondialdehyde (MDA), serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, and hepatocyte apoptosis were significantly decreased in gypenosides groups; while serum high density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD) activity in both serum and hepatic tissue and mRNA and protein level of peroxisome proliferator-activated receptor α (PPAR-α) were significantly increased. Moreover, hepatic steatosis and mitochondrial damage were improved. These results suggested that gypenosides could prevent liver fatty degeneration in fatty liver disease through modulating lipid metabolism, ameliorating liver dysfunction and reducing oxidative stress.
Assuntos
Colesterol na Dieta , Dieta Hiperlipídica , Fígado Gorduroso Alcoólico/prevenção & controle , Fígado Gorduroso/prevenção & controle , Gynostemma , Fígado/efeitos dos fármacos , Preparações de Plantas/farmacologia , Substâncias Protetoras/farmacologia , Alanina Transaminase/sangue , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Colesterol na Dieta/sangue , LDL-Colesterol/sangue , Citoproteção , Modelos Animais de Doenças , Ácidos Graxos não Esterificados/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Fígado Gorduroso Alcoólico/sangue , Fígado Gorduroso Alcoólico/etiologia , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/patologia , Gynostemma/química , Fígado/metabolismo , Fígado/ultraestrutura , Masculino , Malondialdeído/sangue , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica , PPAR alfa/efeitos dos fármacos , PPAR alfa/genética , PPAR alfa/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Preparações de Plantas/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue , Triglicerídeos/sangueRESUMO
We report the fingerprint development of a traditional Chinese medicine Radix Angelicae Dahuricae root and the correlation of the fingerprint peaks with its in vivo pharmacological effects. The high-performance liquid chromatography (HPLC) methods with the computer aided similarity evaluation were validated and used in serial pharmacological studies in mice. The major constituents of R. Angelicae Dahuricae were successfully separated by the HPLC methods, and the effects of sedation and analgesia were mainly related to the chromatographic peaks of group II. The anti-inflammatory, anti-heat stroke and anti-endotoxemic effects were mainly related to the peaks in group III. These results indicated a correlation between the HPLC fingerprints in groups and the pharmacological effects of R. Angelicae Dahuricae. This simple and accurate method can be used for the identification of the active components of R. Angelicae Dahuricae and for the quality control of its pharmaceutical preparations.