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1.
Nat Neurosci ; 11(4): 497-504, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18311133

RESUMO

Changes in visual cortical responses that are induced by monocular visual deprivation are a widely studied example of competitive, experience-dependent neural plasticity. It has been thought that the deprived-eye pathway will fail to compete against the open-eye pathway for limited amounts of brain-derived neurotrophic factor, which acts on TrkB and is needed to sustain effective synaptic connections. We tested this model by using a chemical-genetic approach in mice to inhibit TrkB kinase activity rapidly and specifically during the induction of cortical plasticity in vivo. Contrary to the model, TrkB kinase activity was not required for any of the effects of monocular deprivation. When the deprived eye was re-opened during the critical period, cortical responses to it recovered. This recovery was blocked by TrkB inhibition. These findings suggest a more conventional trophic role for TrkB signaling in the enhancement of responses or growth of new connections, rather than a role in competition.


Assuntos
Receptor trkB/metabolismo , Privação Sensorial/fisiologia , Visão Monocular/fisiologia , Córtex Visual/metabolismo , Vias Visuais/fisiologia , Substituição de Aminoácidos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Lateralidade Funcional/fisiologia , Camundongos , Camundongos Mutantes , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Receptor trkB/genética , Recuperação de Função Fisiológica/fisiologia
2.
Transfusion ; 49(5): 985-94, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19175545

RESUMO

BACKGROUND: It is estimated that approximately 300,000 neonates undergo transfusions annually. The neonatal immune system is immature, making such patients more susceptible to the effects associated with transfusion-transmitted bacteria, viruses, protozoa, and white blood cells (WBCs). The INTERCEPT Blood System is a photochemical process (PCT) utilizing amotosalen and long-wavelength ultraviolet to inactivate pathogens and WBCs in both platelet (PLT) and plasma components for transfusion. A series of clinical studies has shown PCT PLTs and PCT plasma to be safe and effective for transfusion in adults and pediatric patients. Because clinical studies in neonates are technically difficult and ethically challenging, preclinical toxicologic studies were conducted in neonatal rats to evaluate the safety of PCT blood components for neonates. STUDY DESIGN AND METHODS: This study examined daily intravenous administration to neonatal rats of amotosalen in 35 percent:65 percent plasma:InterSol from 1 microg per kg per day (representing 1-unit transfusion) to 457 microg per kg per day (representing multiple transfusions) from Postnatal Day 4 (PND4) to PND31. Rats were observed for viability, clinical signs, and body weights until PND31 and then subjected to pathology evaluation. Hematology, clinical chemistry, and urinalysis data were also collected on PND31. Toxicokinetic parameters were evaluated on PND4 and PND31. RESULTS: There were no amotosalen-related effects on clinical signs, body weight, hematology, clinical chemistry, urinalysis, gross pathology, or histopathology, despite the exposure of neonatal rats to amotosalen concentrations as high as approximately 48 times the standard exposure in adult patients. CONCLUSION: This study demonstrates the safety of PCT for transfusion in neonatal rats and augments data from other studies and clinical use supporting the use of PCT in neonatal patients.


Assuntos
Transfusão de Componentes Sanguíneos/métodos , Transfusão de Plaquetas/métodos , Esterilização/métodos , Animais , Animais Recém-Nascidos , Transfusão de Componentes Sanguíneos/normas , Furocumarinas/toxicidade , Processos Fotoquímicos , Transfusão de Plaquetas/normas , Ratos , Medição de Risco
3.
Neuron ; 36(3): 483-91, 2002 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-12408850

RESUMO

Experience is a powerful sculptor of developing neural connections. In the primary visual cortex (V1), cortical connections are particularly susceptible to the effects of sensory manipulation during a postnatal critical period. At the molecular level, this activity-dependent plasticity requires the transformation of synaptic depolarization into changes in synaptic weight. The molecule alpha calcium-calmodulin kinase type II (alphaCaMKII) is known to play a central role in this transformation. Importantly, alphaCaMKII function is modulated by autophosphorylation, which promotes Ca(2+)-independent kinase activity. Here we show that mice possessing a mutant form of alphaCaMKII that is unable to autophosphorylate show impairments in ocular dominance plasticity. These results confirm the importance of alphaCaMKII in visual cortical plasticity and suggest that synaptic changes induced by monocular deprivation are stored specifically in glutamatergic synapses made onto excitatory neurons.


Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Dominância Ocular/genética , Lateralidade Funcional/genética , Plasticidade Neuronal/genética , Neurônios/enzimologia , Fosforilação , Córtex Visual/enzimologia , Córtex Visual/crescimento & desenvolvimento , Envelhecimento/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Diferenciação Celular/genética , Heterozigoto , Homozigoto , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Mutação/genética , Neurônios/citologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Córtex Visual/citologia
4.
J Morphol ; 274(6): 603-14, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23400942

RESUMO

Although the events of spermiogenesis are commonly studied in amniotes, the amount of research available for Squamata is lacking. Many studies have described the morphological characteristics of mature spermatozoa in squamates, but few detail the ultrastructural changes that occur during spermiogenesis. This study's purpose is to gain a better understanding of the subcellular events of spermatid development within the Imbricate Alligator Lizard, Barisia imbricata. The morphological data presented here represent the first complete ultrastructural study of spermiogenesis within the family Anguidae. Samples of testes from four specimens collected on the northwest side of the Nevado de Toluca, México, were prepared using standard techniques for transmission electron microscopy. Many of the ultrastructural changes occurring during spermiogenesis within B. imbricata are similar to that of other squamates (i.e., early acrosome formation, chromatin condensation, flagella formation, annulus present, and a prominent manchette). However, there are a few unique characteristics within B. imbricata spermatids that to date have not been described during spermiogenesis in other squamates. For example, penetration of the acrosomal granule into the subacrosomal space to form the basal plate of the perforatorium during round spermatid development, the clover-shaped morphology of the developing nuclear fossa of the flagellum, and the bulbous shape to the perforatorium are all unique to the Imbricate Alligator Lizard. These anatomical character differences may be valuable nontraditional data that along with more traditional matrices (such as DNA sequences and gross morphological data) may help elucidate phylogenetic relationships, which are historically considered controversial within Squamata.


Assuntos
Lagartos/anatomia & histologia , Lagartos/fisiologia , Espermátides/ultraestrutura , Espermatogênese , Espermatozoides/ultraestrutura , Acrossomo/ultraestrutura , Animais , Núcleo Celular/ultraestrutura , Masculino , México , Microscopia Eletrônica de Transmissão , Filogenia , Testículo/ultraestrutura
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