Calcium sensing receptor mediated the excessive generation of ß-amyloid peptide induced by hypoxia in vivo and in vitro.

Hypoxia played an important role in the pathogenesis of AD. Hypoxia increased Aß formation, then caused Alzheimer's disease. Calcium sensing receptor (CaSR) was involved in the regulation of cell growth, differentiation, hormonal secretion and other physiological function. Increasing evidence supported CaSR might play a more prominent role in susceptibility to AD, but the role of CaSR in Aß overproduction induced by hypoxia and its mechanisms remain unclear. To investigate whether CaSR mediated the overproduction of Aß induced by hypoxia, immunoblot and immunochemistry were employed to determine the expression of CaSR and BACE1 in hippocampal neurons and tissue and Ca(2+) image system was used to measure [Ca(2+)]i in hippocampal neurons. The content of Aß was detected with ELISA kits. Our research found that hypoxia increased the expression of CaSR in hippocampal neurons and tissue and [Ca(2+)]i in hippocampal neurons. Calhex 231, a selective blocher of CaSR, inhibited the increase in [Ca(2+)]i induced by hypoxia. Hypoxia or GdCl3, an agonist of CaSR, increased the expression of BACE1 in hippocampal neurons and tissue, but Calhex 231 or Xesto C (a selective inhibitor of IP3 receptor) partly prevented hypoxia-induced BACE1 overexpression. Hypoxia or GdCl3 increased the content of Aß42 and Aß40 in hippocampal tissue, however Calhex 231 or Xesto C prevented hypoxia-induced the overproduction of Aß42 and Aß40 partly. Based on the above data, we suggested that hypoxia increased [Ca(2+)]i by elevated CaSR expression to promote BACE1 expression, thereby resulting in the overproduction of Aß42 and Aß40.

Rapidly Gelled Lipoic Acid-Based Supramolecular Hydrogel for 3D Printing of Adhesive Bandage.

Developing a strongly adhesive, easily removable, and robust bandage is valuable in trauma emergencies. Poly(lipoic acid) (PLA)-based adhesives with good mechanical properties have been well-developed through a thermal ring-opening polymerization (ROP) method that is easiness. However, the additive manufacturing of PLA-based adhesives remains a challenge. Herein, α-lipoic acid (LA) and trometamol (Tris) are found to rapidly form a supramolecular hydrogel at room temperature with injectability and 3D printing potential. Meanwhile, the synthesized LA-grafted hyaluronic acid and cellulose nanocrystals are involved not only to optimize the extrusion of 3D printing but also to effectively promote fidelity and prevent the inverse closed-loop depolymerization of PLA in water. The hydrogel bandage exhibits strong adhesion to skin while it can be removed with no residue by water flushing, showing protection to neo-tissue during dressing replacement. The in vivo application of the hydrogel bandage significantly promoted wound healing by closing the wound, forming a physical barrier, and providing an anti-inflammatory effect, showing great potential in future clinical applications.

Neuroplastin 65 modulates anxiety- and depression-like behavior likely through adult hippocampal neurogenesis and central 5-HT activity.

Neuroplastin 65 (Np65) is a brain-specific cell adhesion molecule that is highly expressed in the hippocampus, amygdala, and cortex, regions of the brain that are associated with memory and emotions. However, the role of Np65 in regulation of emotional behavior is still unclear. In the present study, we show that Np65 knock-out (Np65 KO) mice display enhanced anxiety-like behavior, a reduction in some aspects of depressive-like behaviors, and increased sociability and memory. Biochemical investigations revealed that Np65 KO mice show increased adult-born neurons and proliferation in the hippocampus. In addition, the level of 5-hydroxytryptamine (5-HT) in the hippocampus was reduced. The expression of tryptophan hydroxylase 2 in the brainstem and the expression of the 5-HT3A receptor were also decreased. Electrophysiological recordings confirmed an impaired maintenance of long-term potentiation in the hippocampus of Np65 KO mice. Together, our findings uncover a role for Np65 in regulating anxiety- and depressive-like behaviors and suggest that Np65 may be essential for the maintenance of emotional stability, indicating that it might be an attractive potential target for treatment of psychiatric disorders.

Microarray Analysis of Gene Expression Changes in Neuroplastin 65-Knockout Mice: Implications for Abnormal Cognition and Emotional Disorders.

Neuroplastin 65 (Np65) is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout (KO) mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially-expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdh1, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.