Astrocytes respond to various form of CNS insults, comprising brain injury and neuroinflammation, and accruing evidence indicates that they exert important functions during these pathological conditions. Yet, surprisingly little is know about the cellular and metabolic changes underlying reactive astrogliosis. here we demonstrate that, shortly after stab wound of hte neocortex, astrocytes proximal to the lesion undergo a profound alteration ot their mitochondrial network, charachterized by the appearance of fragmented mitochondria, different from astrocytes of non-lesioned areas, which display tubular mitochondria. These changes in mitochondrial architecture went in parallele with the acquisition of typical traits of gliosis, raising the question whether alterations in mitochondrial dynamics are a distinctive feature of the astrocytes' reactive stata. Interestingly, focal application of pro-inflammatory factors such IL-1beta or LPS+IFNgamma was sufficient to elicit similar results in astrocytes of acute slices selectively expressing a mitochondrially targeted GFP. We monitored the dynamics of individula mitochondria and demonstrated that they preferentially undergo fission exclusively in those processes proximal to the source of pro-inflammatory drugs, suggesting the existence of local mitochondrial dynamics during neuroinflammation. In culture, inflamed astrocytes recapitulate the observations obstained in slices: we observed a pattern of mitochondrial fragmentation starting with few hours after inflammation, a localize increase in the production of ROS and the appearance of autophagosomes surrounding fragmented mitochondria, indicative of active mitophagy. Thus, our results suggest that the pro-inflammatory cytokines released following brain injury and during neuroinflammation can directly and locally alter the bioenergetics of individual astrocytes, with potential beneficial or detrimental consequences for neuronal and synaptic viability.
Motori E., Conzelmann K.K., Garthe A., Berninger B., Cantelli Forti G., Angeloni C., et al. (2012). Local rearrangement of mitochondrial networks marks the reactivity of astrocytes toward inflammation. Monaco : (sine nomine).
Local rearrangement of mitochondrial networks marks the reactivity of astrocytes toward inflammation
CANTELLI FORTI, GIORGIO;ANGELONI, CRISTINA;MALAGUTI, MARCO;HRELIA, SILVANA
2012
Abstract
Astrocytes respond to various form of CNS insults, comprising brain injury and neuroinflammation, and accruing evidence indicates that they exert important functions during these pathological conditions. Yet, surprisingly little is know about the cellular and metabolic changes underlying reactive astrogliosis. here we demonstrate that, shortly after stab wound of hte neocortex, astrocytes proximal to the lesion undergo a profound alteration ot their mitochondrial network, charachterized by the appearance of fragmented mitochondria, different from astrocytes of non-lesioned areas, which display tubular mitochondria. These changes in mitochondrial architecture went in parallele with the acquisition of typical traits of gliosis, raising the question whether alterations in mitochondrial dynamics are a distinctive feature of the astrocytes' reactive stata. Interestingly, focal application of pro-inflammatory factors such IL-1beta or LPS+IFNgamma was sufficient to elicit similar results in astrocytes of acute slices selectively expressing a mitochondrially targeted GFP. We monitored the dynamics of individula mitochondria and demonstrated that they preferentially undergo fission exclusively in those processes proximal to the source of pro-inflammatory drugs, suggesting the existence of local mitochondrial dynamics during neuroinflammation. In culture, inflamed astrocytes recapitulate the observations obstained in slices: we observed a pattern of mitochondrial fragmentation starting with few hours after inflammation, a localize increase in the production of ROS and the appearance of autophagosomes surrounding fragmented mitochondria, indicative of active mitophagy. Thus, our results suggest that the pro-inflammatory cytokines released following brain injury and during neuroinflammation can directly and locally alter the bioenergetics of individual astrocytes, with potential beneficial or detrimental consequences for neuronal and synaptic viability.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
