Alterations in the astroglial-vascular interface during neuron degeneration

[摘要] The central nervous system (CNS) requires an adequate vascular supply and a functional blood brain barrier (BBB) for neurotransmission.At the BBB, astroglial cells play an essential role by enwrapping blood vessels and forming an interface that maintains the need of nutrients, oxygen and glucose for neurons to use.Changes in this interface can contribute to the etiology of many diseases.In amyotrophic lateral sclerosis (ALS), although there is loss of cortical and spinal motor neurons, astroglial cells and blood vessel are also affected.To better understand the astroglial-vascular biology in the context of ALS, we examined the normal structure of the astrocytes in the motor cortex and spinal cord in vivo, as well as the changes in their structure during chronic stages of the disease. Specific transgenic astroglia reporter mice, confocal imaging and three-dimensional reconstruction (3D) were used for the analysis. Astrocytes from the spinal cord, but not from motor cortex, acquire their morphology in an age dependant manner.During neurodegeneration, diseased astrocytes from motor cortex did not change morphology.Nevertheless, astroglial cells from the ventral grey matter of the spinal cord show an increase in surface area and volume. They extend filamentous process into other astrocytes territories, present membranous spherical formations and decrease their contact with blood vessels. In addition, a subset of astrocytes acquires a phagocytic role during disease progression.Overall, astroglial cells from the spinal cord reorganize their structure during disease conditions.In addition, vascular irregularities were found in the spinal cord during disease.An increase in vascular density during early stages of ALS was observed and the formation of microglia aggregates close to blood vessels at the same disease state.Although it is not known the mechanism why microglia are recruited and aggregated in certain areas of the ventral spinal cord, we observed these regions are the starting point for microglial activation. Results from this investigation provide a deeper understanding of astroglial cells rearrangements and vascular irregularities in the setting of a neurological disease like ALS.

[发布机构] Johns Hopkins University

[效力级别] glial biology

[关键词] Neurodegeneration;glial biology;blood brain barrier;amyotrophic lateral sclerosis;Neuroscience