Fig. 8: Summary of the main findings.

P2Y1R is upregulated in reactive astrocytes in several neurological disorders such as epilepsy, stroke, Alzheimer’s disease, and traumatic brain injury. The increase in P2Y1R signaling in astrocytes leads to neuronal hyperexcitability by increased expression of IGFBP2, which acts as an excitatory signal on neurons. Our data indicate that the functional phenotype of reactive astrocytes with upregulated P2Y1R-IGFBP2 signaling is shared in several neurological diseases including epilepsy and stroke and may contribute to neuronal hyperexcitability.