Neuronal and astrocytic mitochondrial dynamics as vulnerability factors and targets for neuroprotection

• Tipo: Livro de Atas de Conferência Nacional
• Data: 2009

Autores

Jorge M.A. Oliveira (Autor) FFUP; Gonçalves J (Autor) Outra

Conferência Nacional

11th Meeting of the Portuguese Society for Neuroscience

School of Health Sciences, University of Minho, Braga, Portugal, 3 a 6 de Junho de 2009

Classificação Científica

FOS: Ciências médicas e da saúde > Ciências da saúde

CORDIS: Ciências da Saúde > Neurociências > Neuroquímica ; Ciências da Saúde > Neurociências > Neurofisiologia ; Ciências da Saúde > Ciências farmacológicas

Outras Informações

Resumo (PT): Striatal neurons are particularly vulnerable to neurodegeneration, namely in Huntington’s disease. Previous studies with isolated brain mitochondria suggest that those from striatum are particularly vulnerable to Ca2+ loads. However, because the cellular context was absent, it is unknown whether neuronal and glial mitochondria differ, particularly in their physiological intracellular environment. Here we compared in situ neuronal and glial (astrocytic) mitochondria from striatum and cortex (a less vulnerable region) aiming to understand selective striatal vulnerability and uncover targets for neuroprotection. Cortical and striatal cultures were analyzed by functional fluorescence video microscopy at single cell and single mitochondrion resolution. We measured mitochondrial Ca2+ buffering capacity in intact neurons and astrocytes by means of developing a novel experimental strategy with calibrations for cellular mitochondria concentration and rate of [Ca2+]i elevation. Neuronal processes were analyzed for mitochondrial distribution and trafficking. Mitochondria not only in striatal neurons but also in striatal astrocytes buffered less Ca2+ than their cortical counterparts, affording less protection from Ca2+ induced cell death. Mitochondrial Ca2+ buffering was unaffected by thapsigargin or tacrolimus, excluding a major role for the endoplasmic reticulum or calcineurin in modulating cellular differences. Cyclosporin A (CsA; 1 μM) selectively increased Ca2+ buffering capacity of striatal astrocytes but not of the other cell-types. Although mitochondrial fractional occupation of neurites did not differ, their trafficking was faster in cortical vs. striatal neurons. The increased Ca2+ vulnerability of striatal mitochondria stems from neurons and astrocytes, highlighting vulnerable tripartite synapses where astrocytic mitochondria have increased propensity for CsA-sensitive permeability transition. In vivo CsA neuroprotection may thus be indirect, resulting form astrocytic shielding. The slower mitochondrial trafficking in striatal neurons is a putative target for neuroprotection, as it limits the efficient regulation of Ca2+ buffering and energetic needs of distant processes in the course of neuronal injury. doi: 10.3389/conf.neuro.01.2009.11.041

Abstract (EN): Striatal neurons are particularly vulnerable to neurodegeneration, namely in Huntington’s disease. Previous studies with isolated brain mitochondria suggest that those from striatum are particularly vulnerable to Ca2+ loads. However, because the cellular context was absent, it is unknown whether neuronal and glial mitochondria differ, particularly in their physiological intracellular environment. Here we compared in situ neuronal and glial (astrocytic) mitochondria from striatum and cortex (a less vulnerable region) aiming to understand selective striatal vulnerability and uncover targets for neuroprotection. Cortical and striatal cultures were analyzed by functional fluorescence video microscopy at single cell and single mitochondrion resolution. We measured mitochondrial Ca2+ buffering capacity in intact neurons and astrocytes by means of developing a novel experimental strategy with calibrations for cellular mitochondria concentration and rate of [Ca2+]i elevation. Neuronal processes were analyzed for mitochondrial distribution and trafficking. Mitochondria not only in striatal neurons but also in striatal astrocytes buffered less Ca2+ than their cortical counterparts, affording less protection from Ca2+ induced cell death. Mitochondrial Ca2+ buffering was unaffected by thapsigargin or tacrolimus, excluding a major role for the endoplasmic reticulum or calcineurin in modulating cellular differences. Cyclosporin A (CsA; 1 μM) selectively increased Ca2+ buffering capacity of striatal astrocytes but not of the other cell-types. Although mitochondrial fractional occupation of neurites did not differ, their trafficking was faster in cortical vs. striatal neurons. The increased Ca2+ vulnerability of striatal mitochondria stems from neurons and astrocytes, highlighting vulnerable tripartite synapses where astrocytic mitochondria have increased propensity for CsA-sensitive permeability transition. In vivo CsA neuroprotection may thus be indirect, resulting form astrocytic shielding. The slower mitochondrial trafficking in striatal neurons is a putative target for neuroprotection, as it limits the efficient regulation of Ca2+ buffering and energetic needs of distant processes in the course of neuronal injury. doi: 10.3389/conf.neuro.01.2009.11.041

Idioma: Português

Tipo (Avaliação Docente): Científica