Microglia inversely regulate the level of perineuronal nets with the treatment of lipopolysaccharide and valproic acid

Perineuronal nets (PNNs) are extracellular matrix which mostly surround the inhibitory neurons. They are changed in several brain diseases, such as autism spectrum disorder, but the mechanism of PNNs degradation is still unclear. In this study, we investigated the role of microglial cells in regulating PNNs levels. Specifically, 1 day or 3 days after a single dose of lipopolysaccharide (LPS, 0.25 mg/kg) increased the density of microglia and further reduced the density of PNNs in both hippocampus CA1 and visual cortex. Minocycline, an inhibitor of microglia activation, took effect time-dependently. Minocycline for 7 days before a single LPS injection (0.25 mg/kg) inhibited microglia increase and PNNs loss, but minocycline for 3 days did not work. Finally, in a valproic acid (VPA)-treated autism mouse model, microglia were reduced while PNNs(+) cells were increased in both hippocampus CA1 and visual cortex. In summary, the microglia are involved in the balanced level of PNNs, while in the autism model, the altered level of PNNs might be due to the microglia hypofunction.