biostudies-literatureZhou YNatural Science Foundation of Hubei ProvinceNational Key R&D Program of ChinaNational Natural Science Foundation of ChinaHubei Provincial Natural Science FoundationNational Key Research and Development Program of ChinaScience and Technology Innovation Program of Hunan Provincee02535https://www.ebi.ac.uk/biostudies/studies/S-EPMC12499468biostudies-literatureUnknown12(37)Diabetic encephalopathy (DE) is a severe complication of diabetes characterized by cognitive impairment and synaptic dysfunction, while the underlying mechanisms are not clear. Here, a critical role is identified for death-associated protein kinase 1 (DAPK1) in DE pathogenesis using transgenic and streptozotocin-induced diabetic mouse models. Elevated DAPK1 expression in hippocampal excitatory neurons correlates with cognitive deficits, increases neuronal apoptosis, and disrupts synaptic plasticity. Conditional knockout of DAPK1 in CaMKII-positive neurons significantly mitigates these pathological features, improving cognitive performance and synaptic function. Mechanistically, it is demonstrated that reduced hippocampal microRNA (miR)-216a-5p levels in diabetic mice lead to DAPK1 upregulaAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Epigenetic Regulation of DAPK1 and Netrin-1 Drives Diabetic Encephalopathy.PMC124994682022ZD0211800823250172024JJ7442822611385552022CFA0048240142382371403820300322023AFA0682022RC4044Fan HWLi WLShu KLiu LJZhou YKou JXZheng KHu FChu LLGuo ZXYin JWBrazhe NLiu DXiang ZGZhu LQfalseEpigenetic Regulation of DAPK1 and Netrin-1 Drives Diabetic Encephalopathy.Diabetic encephalopathy (DE) is a severe complication of diabetes characterized by cognitive impairment and synaptic dysfunction, while the underlying mechanisms are not clear. Here, a critical role is identified for death-associated protein kinase 1 (DAPK1) in DE pathogenesis using transgenic and streptozotocin-induced diabetic mouse models. Elevated DAPK1 expression in hippocampal excitatory neurons correlates with cognitive deficits, increases neuronal apoptosis, and disrupts synaptic plasticity. Conditional knockout of DAPK1 in CaMKII-positive neurons significantly mitigates these pathological features, improving cognitive performance and synaptic function. Mechanistically, it is demonstrated that reduced hippocampal microRNA (miR)-216a-5p levels in diabetic mice lead to DAPK1 upregula2025-01-01T00:00:00Z2025 Oct2026-06-04T04:47:24.505Z2026-05-05T03:12:29.306ZS-EPMC124994684078789210.1002/advs.202502535