ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Astrocytic PERK Deficiency Drives Prefrontal Circuit Dysfunction and Depressive-Like Behaviors.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Astrocytic PERK Deficiency Drives Prefrontal Circuit Dysfunction and Depressive-Like Behaviors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Disrupted synapses: prefrontal cortex-reward circuit dysfunction in stress-induced depression-like behaviors.Frontiers in cellular neuroscience · 2026Review
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9 authors.
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Abstract
Major depressive disorder (MDD) is associated with dysfunction in prefrontal cortex (PFC) circuits, yet the glial mechanisms underlying these abnormalities remain unclear. Here, downregulation of the endoplasmic reticulum (ER) stress sensor PERK in PFC astrocytes is identified as a mechanistic contributor to depression-related phenotypes. PERK expression is markedly reduced in PFC astrocytes from individuals with MDD and in two chronic-stress mouse models. Astrocyte-specific PERK deletion in stress-naïve mice is sufficient to induce robust depressive-like behaviors and widespread PFC circuit pathology, including dendritic spine loss, pyramidal neuron hypoactivity, and weakened functional connectivity. Mechanistically, PERK-deficient astrocytes display reduced Nrf2 abundance, dysregulated ER and cytosolic Ca
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