Astrocyte secretes IL-6 to modulate PSD-95 palmitoylation in basolateral amygdala and depression-like behaviors induced by peripheral nerve injury.

Dysfunction of glutamatergic synaptic plasticity in basolateral amygdala (BLA) constitutes a critical pathogenic mechanism underlying the depression-like behaviors induced by chronic pain. Astrocytes serve as an important supporting cell modulating glutamatergic synaptic transmission. Here, we found that peripheral spared nerve injury (SNI) induced astrocyte activation to release IL-6 in BLA. Inhibition of astrocyte activity attenuated SNI-induced IL-6 overexpression and depression-like behaviors. Moreover, SNI enhanced the abundance of DHHC2 in synaptosome and DHHC3 in Golgi apparatus, promoted PSD-95 palmitoylation, and increased the recruitment of GluR1 and NR2B at synapses. Suppression of IL-6 or PSD-95 palmitoylation attenuated the synaptic accumulation of GluR1 and NR2B in BLA and improved depression-like behaviors induced by SNI. Furthermore, IL-6 downstream PI3K increased the expression of DHHC3 in Golgi apparatus and facilitated the interaction of palmitoylated PSD-95 with GluR1 and NR2B at synapses. These findings collectively suggested that SNI activated astrocyte to release IL-6 in BLA, which promoted PSD-95 palmitoylation and enhanced the synaptic trafficking of GluR1 and NR2B, and subsequently mediated the depression-like behaviors induced by nerve injury.

Aggregation-induced bioprobe for plasma membrane-specific imaging and photodynamic cancer cell ablation.

Selective labelling of the plasma membrane (PM) by fluorescence imaging techniques enables an intuitive analysis of cell status together with dynamic changes, and therefore is of great value. We herein disclose a novel carbazole-based probe, CPPPy, that shows aggregation-induced emission (AIE) property and is observed to selectively accumulate at the PM of living cells. Benefiting from its good biocompatibility and PM-targeted specificity, CPPPy can light up the PM of cells by high-resolution imaging even at a low concentration of 200 nM. Simultaneously, CPPPy is capable of generating both singlet oxygen and free radical-dominated species upon visible light irradiation, which further induces irreversible growth inhibition and necrocytosis of tumor cells. This study thus provides new insight into the construction of multifunctional fluorescence probes with PM-specific bioimaging and photodynamic therapy.

Direct [4 + 2] Cycloaddition to Isoquinoline-Fused Porphyrins for Near-Infrared Photodynamic Anticancer Agents.

The synthesis of efficient porphyrin-based photosensitizers with intense near-infrared (NIR) absorption is in high demand for photodynamic therapy (PDT) but remains a challenging task. Herein we show the construction of a type of isoquinoline-fused porphyrins 3 and 4 with an impressive NIR-absorbing capacity. In light of the extraordinary singlet oxygen generation capabilities of 3 upon NIR irradiation, the representative nanoparticles (3a-NPs) assembled show excellent tumoricidal behavior with good biocompatibility in the phototherapeutic window (650-850 nm).