Lipocalin-2 deficiency attenuates kainic acid-induced hippocampal cell death in ...

연구 요약

Lipocalin-2 deficiency attenuates kainic acid-induced hippocampal cell death in a high-fat diet-fed diabetic mice.

Metabolic brain disease 학술지에 발표된 이 연구는 Shin HJ, Kim KE, An HS 외 연구팀이 수행하였습니다.

이 연구는 'Lipocalin-2 deficiency attenuates kainic acid-induced hippocampal cell death in a high-fat diet-fed diabetic mice.'에 대한 과학적 분석을 제공합니다.

핵심 내용

Metabolic dysfunctions such as obesity and diabetes predispose the brain to heightened excitotoxic vulnerability, aggravating neuronal injury and cognitive decline. This study investigated the mechanistic role of lipocalin-2 (LCN2) in metabolic stress-amplified hippocampal damage following kainic acid (KA) exposure. Using high-fat diet (HFD)-fed diabetic wild type (WT) and LCN2 knockout (LCN2KO) mice, we found that LCN2 deficiency improved systemic insulin sensitivity and alleviated hepatic steatosis. In the diabetic hippocampus, LCN2 deletion markedly reduced KA-induced neuronal apoptosis, blood-brain barrier leakage, and iron-mediated oxidative stress. LCN2 ablation suppressed activation of microglia and astrocytes, downregulated galectin-3 and pro-inflammatory cytokines, and inhibited signal transducer and activator of transcription 3 (STAT3)-NF-κBp65-dependent signaling in KA-treated diabetic hippocampus. Reduced autophagy-related protein expression and protein aggregation in KA-treated diabetic LCN2KO mice indicated that LCN2 amplifies excitotoxic stress through autophagic and inflammatory mechanisms. These results identify LCN2 as a pivotal mediator linking metabolic dysfunction to neuroinflammation, ferroptosis, microglial activation, and autophagy in the diabetic hippocampus with excitotoxicity, suggesting that targeting the microglial LCN2-STAT3-NF-κBp65 axis may offer therapeutic potential for metabolic disease-associated acute brain injury.

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