Carboxylated Zn-phthalocyanine attenuates brain Aβ in AD model mouse

Abstract

The deposition of aggregated amyloid β (Aβ) is considered as a key factor for Alzheimer’s Disease (AD). Previously, we demonstrated that a carboxylated Zn-phthalocyanine (ZnPc) inhibits Aβ fibril formation, consequently protects neurons in culture. This study evaluated the effects of ZnPc on pathological changes in an AD mouse model (J20). Nine-month-old J20 mice received weekly intraperitoneal injection of ZnPc (2 and 4 mg/kg) for 12 weeks. Cognitive performance was assessed using Y-maze and open field tests. ZnPc levels in the tissues were evaluated using near-infrared microscopy and spectroscopy. ZnPc accumulated primarily in the liver and kidney. A considerable amount was also detected in brain tissue, where it co-localized with neurons, microglia, and extracellularly deposited Aβ. ZnPc treatment (2 mg/kg) significantly improved cognitive functions of J20 mice. Immunostaining results showed that Aβ was positive intracellularly in neurons, and extracellularly around the vessels and parenchyma in the cortex and hippocampus of PBS-treated J20 mice, which was significantly decreased in ZnPc-treated J20 mice in a dose-dependent manner. Nissl staining demonstrated that neuronal numbers were increased both in the cortex and hippocampus. GFAP-positive astrocytes and Iba-1 positive microglia were decreased by ZnPc treatment. Also, vessel numbers were increased in ZnPc-treated groups. In PBS-treated group, aquaporin 4 immunopositive area extended beyond STL-positive vessels into the parenchyma, which was confined primarily around the vessels in the ZnPc-treated group. Claudin 5 levels were increased in ZnPc-treated group. Therefore, ZnPc can decrease brain Aβ deposition in J20 mice, suggesting it as a potential therapeutic agent for AD.