The Chinese Herbal Formula PAPZ Ameliorates Behavioral Abnormalities in Depressive Mice.

Major depressive disorder (MDD) is a chronic mental disorder characterized by mixed symptoms and complex pathogenesis. With long history of practical application, traditional Chinese medicine (TCM) offers many herbs for the treatment and rehabilitation of chronic disease. In this study, we developed a modified Chinese herbal formula using Panax ginseng, Angelica Sinensis, Polygala tenuifolia Willd, and Ziziphi spinosae Semen (PAPZ), based on an ancient TCM prescription. The antidepressant effects of PAPZ were investigated with a corticosterone (CORT) model of depression in mice. Our results showed that administration of PAPZ ameliorated depression-like phenotypes in the CORT model. An anatomic study showed that chronic PAPZ administration upregulated the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissue. The enzyme activity of superoxide dismutase was enhanced in hippocampal tissue, in line with a decreased malondialdehyde level. Taken together, these findings suggested that PAPZ has therapeutic effects in a mice depression model through increasing protein expression of BDNF and improving the anti-oxidation ability of the brain.

A Direct Quantitative Analysis of Erythrocyte Intracellular Ionized Magnesium in Physiological and Pathological Conditions.

Magnesium (Mg2+) is an endogenous cation that is involved in many essential biological reactions. Abnormal Mg2+ metabolisms in the body affect important physiological and pathological processes. However, most endogenous Mg2+ markers fail to represent body Mg2+ status; they are disadvantageous in terms of representational capacity, applied range, operational convenience, etc. In this article, we evaluated some of the most popular Mg2+ marker candidates. A logical model of the blood Mg2+ compartments was established, which consisted of unstable Mg2+ pools, representative Mg2+ pools, and conserved Mg2+ pools. These pools were based on the metabolic efficiency of Mg2+ in an acute Mg2+ intake test. The results of this study showed that only the erythrocyte intracellular ionized Mg2+ (RBC [Mg2+]i), a representative Mg2+ pool, could effectively represent abnormal body Mg2+ metabolisms in various conditions, including dietary Mg2+ adjustments, aging and metabolic syndrome. These results suggest that RBC [Mg2+]i might be a widely applicable marker of body Mg2+ levels. On unified technology platform and evaluation system, this research compared the representative capacities of RBC [Mg2+]i, plasma Mg2+ concentration (plasma [Mg2+]), erythrocyte intracellular total Mg (RBC [Mg]total) and Mg retention in rats and mice under various Mg2+-metabolism-related physiological and pathological conditions. Our technique for the direct quantitative analysis of RBC [Mg2+]i may prove valuable for basic physiological research, dietary Mg2+ regulation, as well as clinical monitoring/intervention of Mg2+-metabolism-related pathology.

Finite-element reconstruction of 2D circular scanning photoacoustic tomography with detectors in far-field condition.

The finite-element method (FEM) has been a powerful numerical tool for the reconstruction of 2D circular scanning-based photoacoustic tomography (PAT) for its unrivaled ability to accommodate complex boundary conditions, quantitatively reconstruct different physical parameters, and enable low sampling frequency and fewer detector numbers. To reduce the computation cost, a smaller image domain is commonly used instead of the region surrounded by the transducer scanning trace. Then, the pressure data used for the reconstruction that is defined on the boundary of the image domain is usually obtained by directly time delaying the actual measured data. In this case, distortions will be aroused for targets that are away from the rotation center. In this work, we put forward a new data preprocessing method to overcome this problem with a virtual detector concept, in which the measured data for the virtual point detectors on the boundary of the reconstruction domain are generated by a summation of the signals from nearby true detectors. The complete removal of the distortions using our proposed algorithm was proven with experimental reconstruction results.

Calorie restriction is the most reasonable anti-ageing intervention: a meta-analysis of survival curves.

Despite technological advances, the survival records from longevity experiments remain the most indispensable tool in ageing-related research. A variety of interventions, including medications, genetic manipulations and calorie restriction (CR), have been demonstrated to extend the lifespan of several species. Surprisingly, few systematic studies have investigated the differences among these anti-ageing strategies using survival data. Here, we conduct a comprehensive and comparative meta-analysis of numerous published studies on Caenorhabditis elegans and Drosophila. We found that CR and genetic manipulations are generally more effective than medications at extending the total lifespan in both models, and CR can improve the ageing pattern of C. elegans. We further analysed the survival variation for different anti-ageing medications and determined that hypoglycaemic agents and antioxidants are advantageous despite only moderately increasing the overall lifespan; therefore, these two types of medications are promising CR mimetics. Analysis of genetic manipulations also indicated that the genes or pathways that extend lifespan in a healthier pattern are associated with CR. These results suggest that CR or CR mimetics may be the most reasonable and potentially beneficial anti-ageing strategy.

Erythrocyte intracellular Mg(2+) concentration as an index of recognition and memory.

Magnesium (Mg(2+)) plays an important role in the neural system, and yet scarcely any research has quantitatively analyzed the link between endogenous Mg(2+) level and memory. Using our original technique, we measured erythrocyte intracellular ionized Mg(2+) concentration (RBC [Mg(2+)]i), which linearly correlated to recognition and spatial memory in normal aging rats. In the brain, RBC [Mg(2+)]i significantly correlated to hippocampus extracellular fluid Mg(2+) concentration, and further correlated to hippocampal synapse density. Elevation of Mg(2+) intake in aged rats demonstrated an association between RBC [Mg(2+)]i increase and memory recovery. The therapeutic effect of Mg(2+) administration was inversely correlated to individual basal RBC [Mg(2+)]i. In summary, we provide a method to measure RBC [Mg(2+)]i, an ideal indicator of body Mg(2+) level. RBC [Mg(2+)]i represents rodent memory performance in our study, and might further serve as a potential biomarker for clinical differential diagnosis and precise treatment of Mg(2+)-deficiency-associated memory decline during aging.

Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer's disease mouse model.

BACKGROUND: Profound synapse loss is one of the major pathological hallmarks associated with Alzheimer's disease, which might underlie memory impairment. Our previous work demonstrates that magnesium ion is a critical factor in controlling synapse density/plasticity. Here, we tested whether elevation of brain magnesium, using a recently developed compound (magnesium-L-threonate, MgT), can ameliorate the AD-like pathologies and cognitive deficits in the APPswe/PS1dE9 mice, a transgenic mouse model of Alzheimer's disease. RESULTS: MgT treatment reduced Aß-plaque, prevented synapse loss and memory decline in the transgenic mice. Strikingly, MgT treatment was effective even when the treatment was given to the mice at the end-stage of their Alzheimer's disease-like pathological progression. To explore how elevation of brain magnesium ameliorates the AD-like pathologies in the brain of transgenic mice, we studied molecules critical for APP metabolism and signaling pathways implicated in synaptic plasticity/density. In the transgenic mice, the NMDAR signaling pathway was downregulated, while the BACE1 expression were upregulated. MgT treatment prevented the impairment of these signaling pathways, stabilized BACE1 expression and reduced sAPPß and ß-CTF in the transgenic mice. At the molecular level, elevation of extracellular magnesium prevented the high Aß-induced reductions in synaptic NMDARs by preventing calcineurin overactivation in hippocampal slices. CONCLUSIONS: Our results suggest that elevation of brain magnesium exerts substantial synaptoprotective effects in a mouse model of Alzheimer's disease, and hence it might have therapeutic potential for treating Alzheimer's disease.

Elevation of brain magnesium prevents and reverses cognitive deficits and synaptic loss in Alzheimer's disease mouse model.

Profound synapse loss is one of the major pathological hallmarks associated with Alzheimer's disease (AD) and might underlie memory impairment. Our previous work demonstrated that the magnesium ion is a critical factor in controlling synapse density/plasticity. Here, we investigated whether elevation of brain magnesium by the use of a recently developed compound, magnesium-l-threonate (MgT), can ameliorate the AD-like pathologies and cognitive deficits in the APPswe/PS1dE9 mice, a transgenic (Tg) mouse model of AD. MgT treatment reduced Aß plaque and prevented synapse loss and memory decline in the Tg mice. Strikingly, MgT treatment was effective even when given to the mice at the end stage of their AD-like pathological progression. To explore how elevation of brain magnesium ameliorates the AD-like pathologies in the brains of Tg mice, we studied molecules critical for APP metabolism and signaling pathways implicated in synaptic plasticity/density. In the Tg mice, the NMDAR/CREB/BDNF signaling was downregulated, whereas calpain/calcineurin/Cdk5 neurodegenerative signaling and ß-secretase (BACE1) expression were upregulated. MgT treatment prevented the impairment of these signaling pathways, stabilized BACE1 expression, and reduced soluble APPß and ß-C-terminal fragments in the Tg mice. At the molecular level, elevation of extracellular magnesium prevented the high-Aß-induced reductions in synaptic NMDARs by preventing calcineurin overactivation in hippocampal slices. Correlation studies suggested that the protection of NMDAR signaling might underlie the stabilization of BACE1 expression. Our results suggest that elevation of brain magnesium exerts substantial synaptoprotective effects in a mouse model of AD and may have therapeutic potential for treating AD in humans.