Mecanismos molecurales y celulares de la neuroprotección y plasticidad inducida por factor neurotrófico derivado del cerebro
type: CreativeWork
description: [EN]Brain-derived neurotrophic factor (BDNF) is a pro-survival protein, highly expressed in the hippocampus, with critical functions in both developing and adult neurons. BDNF preferentially binds to TrkB receptors activating, in parallel, the Ras-ERK, PI3K/AKT and PLCgamma signaling pathways. Under physiological conditions, BDNF regulates several mechanisms of synaptic plasticiy. Under pathological conditions, BDNF protects hippocampal neurons from glutamate excitotoxicity and ischemia. However, the precise molecular mechanisms BDNF triggers upon TrkB receptor activation to induce neuronal protection and/or recovery are not fully understood. This study sought to address these issues and further examine the possible link between BDNF-induced mechanisms of neuroprotection and/or recovery and mechanisms of synaptic plasticity. In the first part of this study we examined molecular alterations induced by excitotoxicity, focusing on the downregulation of glutamic acid decarboxylase, which likely affects inhibitory synaptic transmission. We found that excitotoxic stimulation of cultured hippocampal neurons with glutamate leads to a time-dependent N-terminal cleavage of glutamic acid decarboxylase isoforms GAD65 and GAD67, upon ubiquitination and degradation of an unknown binding partner by the proteasome. The characteristic punctate distribution of GAD65 along neurites of differentiated cultured hippocampal neurons and total GAD activity measured in cerebellum or cerebral cortex extracts were significantly reduced. The results showed the deregulation of GADs under excitotoxic conditions, which most likely affects GABAergic neurotransmission, upon UPS activity, in addition to other proteolytic systems previously implicated in glutamate-induced excitotoxicity (Please refer to chapter 1). We then further evaluated the differential activation of the three main proteolytic mechanisms (UPS, calpains and caspases) implicated in excitotoxicity. We sought to study the protective e…
abstract: [EN]Brain-derived neurotrophic factor (BDNF) is a pro-survival protein, highly expressed in the hippocampus, with critical functions in both developing and adult neurons. BDNF preferentially binds to TrkB receptors activating, in parallel, the Ras-ERK, PI3K/AKT and PLCgamma signaling pathways. Under physiological conditions, BDNF regulates several mechanisms of synaptic plasticiy. Under pathological conditions, BDNF protects hippocampal neurons from glutamate excitotoxicity and ischemia. However, the precise molecular mechanisms BDNF triggers upon TrkB receptor activation to induce neuronal protection and/or recovery are not fully understood. This study sought to address these issues and further examine the possible link between BDNF-induced mechanisms of neuroprotection and/or recovery and mechanisms of synaptic plasticity. In the first part of this study we examined molecular alterations induced by excitotoxicity, focusing on the downregulation of glutamic acid decarboxylase, which likely affects inhibitory synaptic transmission. We found that excitotoxic stimulation of cultured hippocampal neurons with glutamate leads to a time-dependent N-terminal cleavage of glutamic acid decarboxylase isoforms GAD65 and GAD67, upon ubiquitination and degradation of an unknown binding partner by the proteasome. The characteristic punctate distribution of GAD65 along neurites of differentiated cultured hippocampal neurons and total GAD activity measured in cerebellum or cerebral cortex extracts were significantly reduced. The results showed the deregulation of GADs under excitotoxic conditions, which most likely affects GABAergic neurotransmission, upon UPS activity, in addition to other proteolytic systems previously implicated in glutamate-induced excitotoxicity (Please refer to chapter 1). We then further evaluated the differential activation of the three main proteolytic mechanisms (UPS, calpains and caspases) implicated in excitotoxicity. We sought to study the protective e…
author: Vieira Melo, Carlos Henrique
keywords: Neuroscience, Life sciences, Cell biology, Molecular Biology, Tesis y disertaciones académicas, Universidad de Salamanca (España), Academic dissertations, Neurociencias, Ciencias de la vida, Biología celular, Biología molecular
date published: 2013-05-28
date modified: 2026-07-27T21:03:17Z
provider: Universidad de Salamanca
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Universidad de Salamanca

PropertyValue
property ID: DOI
value: 10.14201/gredos.123071