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HIV-1 transactivator protein (Tat) induces tight junction (TJ) dysfunction and amyloid-beta (Aβ) clearance dysfunction, contributing to the development and progression of HIV-1-associated neurocognitive disorder (HAND). The Rho/ROCK signaling pathway has protective effects on neurodegenerative disease. However, the underlying mechanisms of whether Rho/ROCK protects against HIV-1 Tat-caused dysfunction of TJ and neprilysin (NEP)/Aβ transfer receptor expression have not been elucidated. C57BL/6 mice were administered sterile saline (i.p., 100 μL) or Rho-kinase inhibitor hydroxyfasudil (HF) (i.p., 10 mg/kg) or HIV-1 Tat (i.v., 100 μg/kg) or HF 30 min before being exposed to HIV-1 Tat once a day for seven consecutive days. Evans Blue (EB) leakage was detected via spectrophotometer and brain slides in mouse brains. The protein and mRNA levels of zonula occludens-1 (ZO-1), occludin, NEP, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in mouse brain microvessels were, respectively, analyzed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. Exposure of the mice to HIV-1 Tat increased the amount of EB leakage, EB fluorescence intensity, blood–brain barrier (BBB) permeability, as well as the RAGE protein and mRNA levels, and decreased the protein and mRNA levels of ZO-1, occludin, NEP, and LRP1 in mouse brain microvessels. However, these effects were weakened by Rho-kinase inhibitor HF. Taken together, these results provide information that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-induced dysfunction of TJ and NEP/Aβ transfer receptor expression in the C57BL/6 mouse brain. These findings shed some light on potentiality of inhibiting Rho/Rock signaling pathway in handling HAND.
相似文献In recent decades, the Eurasian beaver (Castor fiber) has once again become the keystone species in small river ecosystems in Russia. In many places, beaver activity has resulted in a significant change in lotic habitats, affecting the diversity, density, and biomass of aquatic organisms, including fish. While many studies have considered the ecosystem impacts of beavers, relatively few have focused on understanding the influence of beaver activity on steppe rivers. We conducted the first quantitative study of beaver impacts on fish assemblages in beaver-influenced and beaver-free sites on two small steppe rivers in the Don River basin in Russia. The presence of beavers altered the habitats in small steppe rivers and affected the diversity, density, and biomass of fish. A comparison of the number of species, density, and biomass of fish in six types of river habitats showed that these parameters were lower in beaver ponds than at riverine sites without beaver activity. Three fish species primarily preferred a single habitat type. Barbatula barbatula was found in riffles, Misgurnus fossilis in old beaver ponds, and Eudontomyzon mariae in abandoned beaver ponds. Beavers impacted fish distribution and density by changing dissolved oxygen, pH, and water current velocity. Overall, our results showed that the presence of beavers led to a temporary homogenization of fish habitats at a local scale in the valleys of small steppe rivers because beavers occupied these rivers only for a short period. However, habitat heterogeneity may increase if the beaver population stays stable or expands in the future.
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