Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy
| Autor: | Paul J. Feustel, Gary W. Mathern, Yunfei Huang, Xiao-Feng Zhao, Matthew A. Adamo, Michael Gruenthal, Xinjun Zhu, Joseph E. Mazurkiewicz, Julia W. Chang, Jiang Qian, Anthony L. Ritaccio, Shannon Morgan, Ramkumar Mathur, Yuan Liao |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Medical Physiology microglia tuberous sclerosis complex Current Literature In Basic Science Hippocampal formation Inbred C57BL Epileptogenesis Tuberous Sclerosis Complex 1 Protein Epilepsy Mice 0302 clinical medicine Recurrence synapse lcsh:QH301-705.5 Mice Knockout Microglia TOR Serine-Threonine Kinases Brain 3. Good health medicine.anatomical_structure lysosome mTOR Female medicine.symptom Inflammation Mediators Chemokines Astrocyte Signal Transduction Knockout seizure Inflammation General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences astrocyte Phagocytosis medicine Animals PI3K/AKT/mTOR pathway Cell Proliferation business.industry medicine.disease Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) inflammation Astrocytes Synapses epilepsy epileptogenesis Biochemistry and Cell Biology business Lysosomes Neuroscience 030217 neurology & neurosurgery Homeostasis Gene Deletion |
| Zdroj: | Cell Reports, Vol 22, Iss 8, Pp 2080-2093 (2018) Cell reports Cell reports, vol 22, iss 8 |
| ISSN: | 2211-1247 |
| Popis: | Summary Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippo-campal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention. Graphical abstract Zhao et al. reveal that elevated mTOR signaling in microglia propels the cells to acquire a noninflammatory reactive-like phenotype, which leads to disruption of CNS homeostasis. The authors also report that reactive-like microglia promote epileptogenesis independent of the inflammatory response. |
| Databáze: | OpenAIRE |
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