RESUMO
While numerous studies have focused on identifying and characterizing the neural mechanisms mediating upper airway defense reflexes in the anesthetized or decerebrate adult cat, little is known about these behaviors in in vivo rodent models. The current study was undertaken to investigate whether the in vivo decelerate adult rat might serve as an acceptable model for studying these behaviors. To begin to address this possibility, we examined multiple respiratory motor activities in response to mechanical stimulation of the anterior nasal cavity (sufficient to elicit fictive sneezing) in in vivo decerebrate adult rats. We found that the neural activities observed during nasal stimulation were consistent with those previously reported during fictive sneezing in the adult cat model. We suggest that the in vivo decerebrate rat is an acceptable model for studying the sneezing reflex.
Assuntos
Abdome/fisiologia , Modelos Biológicos , Movimento , Espirro/fisiologia , Animais , Nervo Hipoglosso/fisiologia , Nervo Frênico/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
Recent work from our laboratory has focused on identifying burst-to-burst variability in temporal and spectral characteristics for 5-minute time series segments of basal inspiratory motor discharges from urethane-anesthetized adult C57BL/6 mice. The current investigation, as the continuation of our previous studies, examined short- and long-term burst-to-burst variability in temporal and spectral components as well as in complexity, which reflects the central respiratory network dynamics. All measures were assessed by quantitative poincaré plot analyses and the determination of the coefficient of variation.
Assuntos
Diafragma/fisiologia , Inalação/fisiologia , Músculos Respiratórios/fisiologia , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Uretana/farmacologia , Anestésicos Intravenosos/farmacologia , Animais , Diafragma/efeitos dos fármacos , Eletromiografia , Feminino , Inalação/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculos Respiratórios/efeitos dos fármacosRESUMO
Activin receptor-like kinase (ALK)7 is a type I serine/threonine kinase receptor of the transforming growth factor (TGF)-beta family of proteins that has similar properties to other type I receptors when activated. To see whether ALK7 can induce apoptosis as can some of the other ALK proteins, we infected the FaO rat hepatoma cell line with adenovirus expressing a constitutively active form of the ALK7. Cells infected with active ALK7 adenovirus showed an apoptotic-positive phenotype, as opposed to those that were infected with a control protein. DNA fragmentation assays and fluorescence-activated cell sorter analysis also indicated that ALK7 infection induced apoptosis in FaO cells. We also confirmed this finding in Hep3B human hepatoma cells by transiently transfecting the constitutively active form of ALK7, ALK7(T194D). Investigation into the downstream targets and mechanisms involved in ALK7-induced apoptosis revealed that the TGF-beta signaling intermediates, Smad2 and -3, were activated, as well as the MAPKs JNK and p38. In addition, caspase-3 and -9 were also activated, and cytochrome c release from the mitochondria was observed. Short interfering RNA-mediated inhibition of Smad3 markedly suppressed ALK7-induced caspase-3 activation. Treatment with protein synthesis inhibitors or the expression of the dominant-negative form of the stress-activated protein/extracellular signal-regulated kinase 1 abolished not only JNK activation but apoptosis as well. Taken together, these results suggest that ALK7 induces apoptosis through activation of the traditional TGF-beta pathway components, thus resulting in new gene transcription and JNK and p38 activation that initiates cross-talk with the cellular stress death pathway and ultimately leads to apoptosis.