What does this research mean for the field?

The P2Y1R-IGFBP2 signaling axis in reactive astrocytes drives neuronal hyperexcitability and serves as a common pathogenic mechanism across neurological disorders such as epilepsy and stroke. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine the downstream molecular mechanisms by which P2Y1 receptor upregulation in reactive astrocytes drives neuronal dysfunction in neurological disorders.

September 3, 2026Folia Pharmacologica Japonica

Gq-GPCR upregulation in reactive astrocytes: implication for neurological disorders

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To determine the downstream molecular mechanisms by which P2Y1 receptor upregulation in reactive astrocytes drives neuronal dysfunction in neurological disorders.
Generated transgenic mouse models with astrocyte-specific overexpression of the Gq-coupled purinergic receptor P2Y1R.
Assessed neuronal hyperexcitability and seizure susceptibility using electrophysiology, electroencephalogram recordings, and pilocarpine-induced status epilepticus assays.
Employed calcium imaging, transcriptomic profiling, immunohistochemistry, and astrocyte-specific genome editing to identify and validate downstream effector molecules in epilepsy and cerebral ischemia models.
Astrocyte-specific P2Y1R overexpression induced marked neuronal hyperexcitability, characterized by elevated hippocampal neuronal firing rates, abnormal electroencephalographic spikes, and increased vulnerability to pilocarpine-induced status epilepticus.
Mechanistic profiling identified the secreted factor IGFBP2 as the primary downstream astrocytic effector promoting neuronal hyperexcitation.
Both P2Y1R and IGFBP2 were consistently upregulated in reactive astrocytes within experimental models of epilepsy and cerebral infarction, establishing a conserved disease pathway.

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Implication

Preclinical study demonstrates that astrocytic P2Y1R upregulation drives neuronal hyperexcitability via IGFBP2 in mice, highlighting a shared pathological axis across brain disorders.

Cite This Study

Shigetomi et al. (2026) studied this question.

synapsesocial.com/papers/6a9934b4636c6408cfa7c77e https://doi.org/10.1254/fpj.26045

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Implication

Preclinical study demonstrates that astrocytic P2Y1R upregulation drives neuronal hyperexcitability via IGFBP2 in mice, highlighting a shared pathological axis across brain disorders.

Gq-GPCR upregulation in reactive astrocytes: implication for neurological disorders

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Discussion

Implication

Cite This Study

Gq-GPCR upregulation in reactive astrocytes: implication for neurological disorders

Key Points

Discussion

Implication

Cite This Study

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