Microglial galectin-3 disrupts parvalbumin interneurons and hippocampal synchrony, driving cognitive deficits - PubMed
4 hours ago
- #Cognitive Deficits
- #Neuroinflammation
- #Galectin-3
- Microglial galectin-3 (Gal-3) is identified as a key mediator in sepsis-associated encephalopathy (SAE), driving cognitive impairment through neuroinflammation.
- Systemic inflammation upregulates microglial Gal-3, which activates TLR2 signaling and promotes NLRP3/AIM2 inflammasome assembly, exacerbating oxidative stress.
- This inflammatory cascade selectively damages hippocampal parvalbumin (PV) interneurons, disrupting theta/gamma oscillations and excitatory/inhibitory balance, leading to cognitive deficits.
- Pharmacological inhibition of Gal-3 with TD139 suppresses this pathway and prevents memory deficits, while overexpression of Gal-3 in microglia replicates the cognitive impairments.
- Chemogenetic reactivation of PV interneurons restores hippocampal oscillations and improves cognitive function, highlighting Gal-3 as a potential therapeutic target for inflammation-related cognitive disorders.