Dietary Xylitol Supplement Ameliorated AD-related Neuronal Injury by Regulating Glucose Metabolism Relevant Amino Acids in Mice.

BACKGROUND: Alzheimer's disease (AD) is one of the most common irreversible degenerative diseases of the central nervous system. Recent studies have found that patients with AD generally experience abnormal glucose metabolism. Xylitol is a functional sugar alcohol, which has been reported to regulate glucose metabolism. OBJECTIVE: The present study was designed to determine whether xylitol can alleviate cognitive impairment in AD mice. METHODS: In the current research, 5% xylitol was supplemented in the diet to treat APP/PS1 transgenic AD mice for 2 months. Cognitive ability was measured by the Morris water maze, and anxiety-like behaviors were examined by open-field experiment. Hippocampal cellular apoptosis and mitochondria pathway related apoptotic proteins were tested by TUNEL staining and immunoblotting, respectively. By LC-MS, plasma levels of glucose metabolism intermediates and related amino acids were evaluated. RESULTS: Results showed that xylitol could significantly ameliorate anxiety-like activity in AD mice by partially regulating expression levels of mitochondrial pathway-related apoptotic proteins. Xylitolregulated glucose metabolism may play an important role in the process. CONCLUSION: The current study suggests that xylitol may be a potential candidate for improving neuropsychiatric behavior in AD by regulating the levels of TCA cycle intermediates and related amino acids in glucose metabolism.

Methylcobalamin Alleviates Neuronal Apoptosis and Cognitive Decline Induced by PM2.5 Exposure in Mice.

BACKGROUND: Fine particulate matter (particulate matter 2.5, PM2.5) is considered one of the harmful factors to neuronal functions. Apoptosis is one of the mechanisms of neuronal injury induced by PM2.5. Methylcobalamine (MeCbl) has been shown to have anti-apoptotic and neuroprotective effects. OBJECTIVE: The current work tried to explore the neuroprotective effects and mechanisms that MeCbl protects mice against cognitive impairment and neuronal apoptosis induced by chronic real-time PM2.5 exposure. METHODS: Twenty-four 6-week-old male C57BL/6 mice were exposed to ambient PM2.5 and fed with MeCbl for 6 months. Morris water maze was used to evaluate the changes of spatial learning and memory ability in mice. PC12 cells and primary hippocampal neurons were applied as the in vitro model. Cell viability, cellular reactive oxygen species (ROS) and the expressions of apoptosis-related proteins were examined. And cells were stained with JC-1 and mitochondrial membrane potential was evaluated. RESULTS: In C57BL/6 mice, MeCbl supplementation alleviated cognitive impairment and apoptosis-related protein expression induced by PM2.5 exposure. In in vitro cell model, MeCbl supplementation could effectively rescue the downregulation of cell viability induced by PM2.5, and inhibited the increased levels of ROS, cellular apoptosis, and the expressions of apoptosis related proteins related to PM2.5 treatment, which may be associated with modulation of mitochondrial function. CONCLUSION: MeCbl treatment alleviated cognitive impairment and neuronal apoptosis induced by PM2.5 both in vivo and in vitro. The mechanism for the neuroprotective effects of MeCbl may at least be partially dependent on the regulation of mitochondrial apoptosis.

S-adenosylmethionine decarboxylase 1 and its related spermidine synthesis mediate PM2.5 exposure-induced neuronal apoptosis.

PM2.5 exposure is considered harmful to central nerve system, while the specific biochemical mechanism underlying is still unrevealed. Neuronal apoptosis is believed the crucial event in pathogenesis of neurodegenerative diseases, but evidence supporting neuronal apoptosis as the mechanism for PM2.5 exposure induced neuronal injury is insufficient. S-adenosylmethionine decarboxylase 1 (AMD1) and its related spermidine synthesis have been shown to associate with cellular apoptosis, but its role in PM2.5 exposure induced neuronal apoptosis was rarely reported. The current study was aimed to better understand contribution of AMD1 activity and spermidine in PM2.5 exposure induced neuronal apoptosis. Sixteen C57BL/6 male mice were randomly divided and kept into ambient PM2.5 chamber or filtered air chamber for 6 months to establish the mouse model of whole-body ambient PM2.5 chronic exposure. In parallel, PC12 cells and primary hippocampal neurons were applied for various concentrations of PM2.5 treatment (0, 25, 50, 100, 200, and 400 µg/mL) to explore the possible cellular and molecular mechanism which may be critically involved in the process. Results showed that PM2.5 exposure triggered neuronal apoptosis with increased expression of Bax/Bcl-2 and cleaved caspase-3. PM2.5 exposure reduced AMD1 expression and spermidine synthesis. AMD1 inhibition could mimic PM2.5 exposure induced neuronal apoptosis. Spermidine supplementation rescued against neurotoxicity and inhibited PM2.5 induced apoptosis via impaired depolarization of mitochondrial membrane potential and reduced mitochondrial apoptosis related proteins. In summary, our work demonstrated that exposure to PM2.5 led to neuronal apoptosis, which may be the key event in the process of air pollution induced neurodegenerative diseases. AMD1 and spermidine associated with neuronal apoptosis induced by PM2.5 exposure, which was at least partially dependent on mitochondria mediated pathway.