Search

A promising strategy for the prevention of Alzheimer's disease (AD) is the identification of age-related changes that place the brain at risk for the disease. Additionally, AD is associated with chronic dehydration, and one of the significant changes that are known to result in metabolic dysfunction is an increase in the endogenous formaldehyde (FA) level. Here, we demonstrate that the levels of uric formaldehyde in AD patients were markedly increased compared with normal controls. The brain formaldehyde levels of wild-type C57 BL/6 mice increased with age, and these increases were followed by decreases in their drinking frequency and water intake. The serum arginine vasopressin (AVP) concentrations were also maintained at a high level in the 10-month-old mice. An intravenous injection of AVP into the tail induced decreases in the drinking frequency and water intake in the mice, and these decreases were associated with increases in brain formaldehyde levels. An ELISA assay revealed that the AVP injection increased both the protein level and the enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO), which is an enzyme that produces formaldehyde. In contrast, the intraperitoneal injection of formaldehyde increased the serum AVP level by increasing the angiotensin II (ANG II) level, and this change was associated with a marked decrease in water intake behavior. These data suggest that the interaction between formaldehyde and AVP affects the water intake behaviors of mice. Furthermore, the highest concentration of formaldehyde in vivo was observed in the morning. Regular water intake is conducive to eliminating endogenous formaldehyde from the human body, particularly when water is consumed in the morning. Establishing good water intake habits not only effectively eliminates excess formaldehyde and other metabolic products but is also expected to yield valuable approaches to reducing the risk of AD prior to the onset of the disease.

Living organisms are exposed to the geomagnetic field (GMF) throughout their lifespan. Elimination of the GMF, resulting in a hypogeomagnetic field (HMF), leads to central nervous system dysfunction and abnormal development in animals. However, the cellular mechanisms underlying these effects have not been identified so far. Here, we show that exposure to an HMF (

Our former studies have suggested that TongLuoJiuNao (TLJN) is clinically efficacious in the treatment of dementia and improving learning and memory in AD models. When Aβaggregated with oligomer, it is known to be able to induce cellular toxicity as well as cognitive impairment. We tested the possibility that TLJN affects the formation of Aβoligomers. In our experiment, TLJN improved cell viability, inhibited LDH release, and promoted the outgrowth of neurites of neurons treated with Aβ. Geniposide, the main component of TLJN, could increase the cell viability of SY5Y-APP695sw cells. The cytotoxicity of pretreated Aβwith geniposide was decreased in a dose-dependent manner. SDS-PAGE and Western blotting showed that geniposide and TLJN stimulated Aβoligomer assembly. Compared with the control, more and longer fibrils of Aβin the presence of geniposide were observed under electron microscope though the fibrils became less sensitive to thioflavin T staining. In sum, geniposide is able to protect neurons from Aβ-induced damage by remodeling Aβ.

It has been reported that miR-124a is abundant in the central nervous system including the eye, and is related to neurogenesis in several species. However, the role of miR-124a in the eye remains unclear. In this study, we show that the expression of miR-124a in Xenopus laevis begins along the neural fold, including the protruding eye anlagen, at a low level at around stage 18; its expression level gradually increases in the neural tube and the eye as embryos develop into later stages and then maintains at a high level in eye to adult stages. Microinjection of a miR-124a precursor at the 8-cell stage leads to malformation of the optic nerve and optic cup, indicating the importance of maintaining low levels of miR-124a during early embryonic development. In addition, miR-124a overexpression markedly down regulates the expression of its predicted targets Lhx2, Hairy2, Gli3, NeuroD1 and Otx2 in/around the eye anlagen, and the interaction of miR-124a with the 3′ UTR of Lhx2 represses gene expression as shown by luciferase assays. Moreover, excess miR-124a inhibits cell proliferation in the eye of Xenopus embryos during retinogenesis. These results indicate that miR-124a acts as a post-transcriptional regulator in the genetic network controlling eye morphogenesis and neurogenesis. The mechanism of miR-124a’s early interaction with the genetic network may also persist in its later role in the maturing and adult eye and brain.

Background Formaldehyde can induce misfolding and aggregation of Tau protein and β amyloid protein, which are characteristic pathological features of Alzheimer’s disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline. Methods In this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored. Results Cell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment. Conclusions Our results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione peroxidase.