Abnormal Ca Signals in Reactive Astrocytes as a Common Cause of Brain Diseases.

In pathological brain conditions, glial cells become reactive and show a variety of responses. We examined Ca signals in pathological brains and found that reactive astrocytes share abnormal Ca signals, even in different types of diseases. In a neuropathic pain model, astrocytes in the primary sensory cortex became reactive and showed frequent Ca signals, resulting in the production of synaptogenic molecules, which led to misconnections of tactile and pain networks in the sensory cortex, thus causing neuropathic pain. In an epileptogenic model, hippocampal astrocytes also became reactive and showed frequent Ca signals. In an Alexander disease (AxD) model, -R239H knock-in mice showed accumulation of Rosenthal fibers, a typical pathological marker of AxD, and excessively large Ca signals. Because the abnormal astrocytic Ca signals observed in the above three disease models are dependent on type II inositol 1,4,5-trisphosphate receptors (IPRII), we reanalyzed these pathological events using IPRII-deficient mice and found that all abnormal Ca signals and pathologies were markedly reduced. These findings indicate that abnormal Ca signaling is not only a consequence but may also be greatly involved in the cause of these diseases. Abnormal Ca signals in reactive astrocytes may represent an underlying pathology common to multiple diseases.