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1.
Exp Brain Res ; 199(3-4): 265-78, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19139860

RESUMO

The synRas transgenic mice express constitutively activated Valin12-Harvey Ras in postnatal neocortical pyramidal neurons. This leads to somatodendritic hypertrophy, higher densities of spines and synapses, and an enhancement of synaptic long-term potentiation associated with an increased glutamate receptor-mediated activity. It was less clear how the interneurons respond to these alterations, and this prompted the quantitative assessment of interneuron neurochemistry. Interneurons rarely expressed the transgene, however, several interneuron types displayed a transient somatic hypertrophy. Furthermore, NPY mRNA expression was persistently increased as were the laminar percentages of labeled neurons. The expression of parvalbumin and voltage-gated potassium channels Kv3.1b/3.2 was unchanged. A significant decline of GAD-67, but not GAD-65, mRNA expressing neurons was observed in layer VI in animals older than P60. This suggested that subtle deficits in inhibition and enhanced excitation evoke the interneuronal changes in the synRastransgenic mouse cortex.


Assuntos
Regulação da Expressão Gênica , Interneurônios/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/biossíntese , Córtex Visual/metabolismo , Fatores Etários , Animais , Crescimento Celular , Dendritos/genética , Dendritos/metabolismo , Inibidores do Crescimento/genética , Interneurônios/citologia , Interneurônios/patologia , Camundongos , Camundongos Transgênicos , Inibição Neural/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Córtex Visual/citologia , Córtex Visual/patologia
2.
Brain Struct Funct ; 220(4): 1935-50, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24728870

RESUMO

The 30-amino acid peptide Y-P30, generated from the N-terminus of the human dermcidin precursor protein, has been found to promote neuronal survival, cell migration and neurite outgrowth by enhancing the interaction of pleiotrophin and syndecan-3. We now show that Y-P30 activates Src kinase and extracellular signal-regulated kinase (ERK). Y-P30 promotes axonal growth of mouse embryonic stem cell-derived neurons, embryonic mouse spinal cord motoneurons, perinatal rat retinal neurons, and rat cortical neurons. Y-P30-mediated axon growth was dependent on heparan sulfate chains. Y-P30 decreased the proportion of collapsing/degenerating growth cones of cortical axons in an Src and ERK-dependent manner. Y-P30 increased for 90 min in axonal growth cones the level of Tyr418-phosphorylated Src kinase and the amount of F-actin, and transiently the level of Tyr-phosphorylated ERK. Levels of total Src kinase, actin, GAP-43, cortactin and the glutamate receptor subunit GluN2B were not altered. When exposed to semaphorin-3a, Y-P30 protected a significant fraction of growth cones of cortical neurons from collapse. These results suggest that Y-P30 promotes axonal growth via Src- and ERK-dependent mechanisms which stabilize growth cones and confer resistance to collapsing factors.


Assuntos
Axônios/efeitos dos fármacos , Cones de Crescimento/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Neurônios/citologia , Peptídeos/farmacologia , Actinas/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Embrião de Mamíferos , Proteína GAP-43/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Imagem Molecular , Neurônios/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Ratos , Ratos Long-Evans , Retina/citologia , Retina/efeitos dos fármacos , Semaforina-3A/metabolismo
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