Hydrogen-rich water ameliorates neuropathological impairments in a mouse model of Alzheimer's disease through reducing neuroinflammation and modulating intestinal microbiota.

Hydrogen exhibits the potential to treat Alzheimer's disease. Stereotactic injection has been previously used as an invasive method of administering active hydrogen, but this method has limitations in clinical practice. In this study, triple transgenic (3×Tg) Alzheimer's disease mice were treated with hydrogen-rich water for 7 months. The results showed that hydrogen-rich water prevented synaptic loss and neuronal death, inhibited senile plaques, and reduced hyperphosphorylated tau and neurofibrillary tangles in 3×Tg Alzheimer's disease mice. In addition, hydrogen-rich water improved brain energy metabolism disorders and intestinal flora imbalances and reduced inflammatory reactions. These findings suggest that hydrogen-rich water is an effective hydrogen donor that can treat Alzheimer's disease. This study was approved by the Animal Ethics and Welfare Committee of Shenzhen University, China (approval No. AEWC-20140615-002) on June 15, 2014.

His-Rich Domain of Selenoprotein P Ameliorates Neuropathology and Cognitive Deficits by Regulating TrkB Pathway and Zinc Homeostasis in an Alzheimer Model of Mice.

Selenoproteins are a family of special proteins that contain the 21st amino acid, selenocysteine (Sec), in their sequence. Selenoprotein P has 10 Sec residues and modulates selenium homeostasis and redox balance in the brain. Previously, we found that the Sec-devoid His-rich motif of selenoprotein P (Selenop-H) suppressed metal-induced aggregation and neurotoxicities of both Aß and tau in vitro. To investigate the intervening capacity of Selenop-H on the neuropathology and cognitive deficits of triple transgenic AD (3 × Tg-AD) mice, the Selenop-H gene packaged in rAAV9 was delivered into the hippocampal CA3 regions of mice via stereotaxic injection. Four months later, we demonstrated that Selenop-H (1) improved the spatial learning and memory deficits, (2) alleviated neuron damage and synaptic protein loss, (3) inhibited both tau pathology and amyloid beta protein (Aß) aggregation, (4) activated both BDNF- and Src-mediated TrkB signaling, and (5) increased MT3 and ZnT3 levels and restored Zn2+ homeostasis in the mice model of AD. The study revealed that Selenop-H is potent in ameliorating AD-related neuropathology and cognitive deficits by modulating TrkB signaling and Zn2+ homeostasis.

Sustained release of bioactive hydrogen by Pd hydride nanoparticles overcomes Alzheimer's disease.

Oxidative stress-induced mitochondrial dysfunction plays an important role in the pathogenesis of Alzheimer's disease (AD). Hydrogen molecule, a special antioxidant, can selectively scavenge highly cytotoxic reactive oxygen species such as ·OH, exhibiting a potential to treat AD by reducing oxidative stress. However, there is no effective route to realize the continuous and efficient accumulation of administrated hydrogen in AD brain owing to its low solubility. Here, we develop the small-sized Pd hydride (PdH) nanoparticles for high payload of hydrogen and in situ sustained hydrogen release in AD brain. By virtue of the catalytic hydrogenation effect of Pd, the released hydrogen from PdH nanoparticles exhibits high bio-reductivity in favor of effectively scavenging cytotoxic ·OH in a self-catalysis way. Bio-reductive hydrogen is able to recover mitochondrial dysfunction, inhibit Aß generation and aggregation, block synaptic and neuronal apoptosis and promote neuronal energy metabolism by eliminating oxidative stress and activating the anti-oxidative pathway, consequently ameliorating the cognitive impairment in AD mice. The proposed hydrogen-releasing nanomedicine strategy would open a new window for the treatment of AD.