Search

Anxiety disorder is one of the most common mental disorders worldwide, affecting nearly 30% of adults. However, its underlying molecular mechanisms are still unclear. Here we subjected mice to chronic restraint stress (CRS), a paradigm known to induce anxiety-like behavior in mice. CRS mice exhibited anxiety-like behavior and reduced synaptic transmission in the medial prefrontal cortex (mPFC). Notably, Wisteria Floribunda agglutinin (WFA) staining showed a reduction of perineuronal nets (PNNs) expression in the mPFC of CRS mice. And the mRNA and protein levels of aggrecan (ACAN), a core component of PNNs, were also reduced. Parallelly, enzymatic digestion of PNNs in the mPFC by injecting Chondroitinase ABC (chABC) resulted in anxiety-like behavior in mice. Fluoxetine (FXT) is a clinically prescribed antidepressant/anxiolytic drug. FXT treatment in CRS mice not only ameliorated their deficits in behavior and synaptic transmissions, but also prevented CRS-induced reduction of PNNs and ACAN expressions. This study demonstrates that proper PNNs level is critical to brain functions, and their decline may serve as a pathological mechanism of anxiety disorders. [ABSTRACT FROM AUTHOR]

The article discusses a study by M. Hruska et al which provided evidence that ephrin B-3 controls the synaptic localization and stability of PSD-95 using super resolution imaging to show that ephrin-B3 and PSD-95 colocalize at 80% of synapses in excitatory neurons. They showed that ephrin-B3 is necessary to maintain normal levels of PSD-95 at synapses and posit a working model where nueronal activity stimulates ERK which phosphorylates ephrin-B3.