Journal
NEUROPHARMACOLOGY
Volume 225, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2022.109382
Keywords
Perineuronal net; Parvalbumin interneuron; Cognitive impairments; Lipopolysaccharide
Categories
Ask authors/readers for more resources
This study reveals that active MMP-9 mediates PNN remodeling, leading to reduced synaptic input and abnormal gamma oscillations in hippocampal CA1, ultimately contributing to cognitive impairments in SAE induced by LPS injection. Treatment with the MMP-9 inhibitor SB-3CT can rescue most of these abnormalities.
Sepsis-associated encephalopathy (SAE) is commonly defined as diffuse brain dysfunction and can manifest as delirium to coma. Accumulating evidence has suggested that perineuronal net (PNN) plays an important role in the modulation of the synaptic plasticity of central nervous system. We here investigated the role of PNN in SAE induced by lipopolysaccharide (LPS) injection. Behavioral tests were performed by open field, Y-maze, and fear conditioning tests at the indicated time points. The densities of vesicular gamma-aminobutyric acid transporter, ve-sicular glutamate transporter 1, PNN, and parvalbumin (PV) in the hippocampus were evaluated by immuno-fluorescence. Matrix metalloproteinases-9 (MMP-9) expression and its activity were detected by Western blot and gel zymography, respectively. Local field potential was recorded by in vivo electrophysiology. LPS-treated mice displayed significant cognitive impairments, coincided with activated MMP-9, decreased PNN and PV densities, reduced inhibitory and excitatory input onto PV interneurons enwrapped by PNN, and decreased gamma os-cillations in hippocampal CA1. Notably, MMP-9 inhibitor SB-3CT treatment rescued most of these abnormalities. Taken together, our study demonstrates that active MMP-9 mediated PNN remodeling, leading to reduced inhibitory and excitatory input onto PV interneurons and abnormal gamma oscillations in hippocampal CA1, which consequently contributed to cognitive impairments after LPS injection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available