Neurotoxic reactive astrocytes are induced by activated microglia :

"Reactive astrocytes are strongly induced by central nervous system (CNS) injury and disease, but their role is poorly understood. Here we show that a subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia. We show that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes. A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes. Death of axotomized CNS neurons in vivo is prevented when the formation of A1 astrocytes is blocked. Finally, we show that A1 astrocytes are abundant in various human neurodegenerative diseases including Alzheimer’s, Huntington’s and Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. Taken together these findings help to explain why CNS neurons die after axotomy, strongly suggest that A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders, and provide opportunities for the development of new treatments for these diseases."



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Neurotoxic reactive astrocytes are induced by activated microglia : Nature : Nature Research

Reactive astrocytes are strongly induced by central nervous system (CNS) injury and disease, but their role is poorly understood. Here we show that a subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia. We show that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes. A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes. Death of axotomized CNS neurons in vivo is prevented when the formation of A1 astrocytes is blocked. Finally, we show that A1 astrocytes are abundant in various human neurodegenerative diseases including Alzheimer’s, Huntington’s and Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. Taken together these findings help to explain why CNS neurons die after axotomy, strongly suggest that A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders, and provide opportunities for the development of new treatments for these diseases.



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Glia, not neurons, are most affected by brain aging

The difference between an old brain and a young brain isn't so much the number of neurons but the presence and function of supporting cells called glia. In Cell Reports on January 10, researchers who examined postmortem brain samples from 480 individuals ranging in age from 16 to 106 found that the state of someone's glia is so consistent through the years that it can be used to predict someone's age. The work lays the foundation to better understand glia's role in late-in-life brain disease.

Specific Glial Functions Contribute to Schizophrenia Susceptibility.

 Schizophrenia is a highly polygenic brain disorder. The main hypothesis for disease etiology in schizophrenia primarily focuses on the role of dysfunctional synaptic transmission. Previous studies have therefore directed their investigations toward the role of neuronal dysfunction. However, recent studies have shown that apart from neurons, glial cells also play a major role in synaptic transmission. Therefore, we investigated the potential causal involvement of the 3 principle glial cell lineages in risk to schizophrenia. We performed a functional gene set analysis to test for the combined effects of genetic variants in glial type-specific genes for association with schizophrenia. We used genome-wide association data from the largest schizophrenia sample to date, including 13 689 cases and 18 226 healthy controls. Our results show that astrocyte and oligodendrocyte gene sets, but not microglia gene sets, are associated with an increased risk for schizophrenia. The astrocyte and oligodendrocyte findings are related to astrocyte signaling at the synapse, myelin membrane integrity, glial development, and epigenetic control. Together, these results show that genetic alterations underlying specific glial cell type functions increase susceptibility to schizophrenia and provide evidence that the neuronal hypothesis of schizophrenia should be extended to include the role of glia.

Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair

Astrocytes, the most abundant cell population in the central nervous system (CNS), are essential for normal neurological function. We show that astrocytes are allocated to spatial domains in mouse spinal cord and brain in accordance with their embryonic sites of origin in the ventricular zone. These domains remain stable throughout life without evidence of secondary tangential migration, even after acute CNS injury. Domain-specific depletion of astrocytes in ventral spinal cord resulted in abnormal motor neuron synaptogenesis, which was not rescued by immigration of astrocytes from adjoining regions. Our findings demonstrate that region-restricted astrocyte allocation is a general CNS phenomenon and reveal intrinsic limitations of the astroglial response to injury.