Effects of Ginseng Protein on Gut Microbiota and BDNF/TrkB Signaling Pathway in Alzheimer s Disease Mice

[Objectives] To investigate the effects of ginseng protein on gut microbiota and BDNF/TrkB signaling pathway in Alzheimer s disease (AD) mice. [Methods] D-galactose/AlCl 3 co-induction was used to establish AD model, and mice were randomly divided into normal group 1, normal group 2, model group 1, model group 2, ginseng protein group, and microbiota transplantation group. Morris water maze experiment was used to evaluate learning and memory ability, and Western blot method was used to detect the expression of APP, p-Tau, BDNF, TrkB, p-TrkB proteins in brain tissue, and 16S rDNA was used to detect diversity of fecal microbiota. [Results] Ginseng protein and microbiota transplantation can shorten the escape latency of mice ( P <0.05), increase the number of crossing platforms ( P <0.05), reduce the expression of APP and p-Tau proteins in brain tissue ( P <0.05, P <0.01), increase the expression of BDNF, p-TrkB, p-TrkB/TrkB proteins ( P <0.05, P <0.01), and reduce the abundance of Alloprevotella, Ruminococcaceae _UCG-014, Prevotellaceae _UCG-001, and Ruminococcus _1 ( P <0.05, P <0.01). [Conclusions] The action mechanism of ginseng protein anti AD may be through regulating gut microbiota diversity and activating the BDNF/TrkB signaling pathway.

ω-3PUFAs Prevent MK-801-induced Cognitive Impairment in Schizophrenic Rats via the CREB/BDNF/TrkB Pathway

This study was to determine the protective effect of ω-3 polyunsaturated fatty acids（ω-3PUFAs） on MK-801-induced cognitive impairment in schizophrenia（SZ） rats and the underlying mechanism. A rat model of schizophrenia was induced by MK-801. The cognitive function of rats was assessed using a Morris water maze. The number of hippocampal neurons was measured by Nissl staining. The expression of CREB, p-CREB, BDNF, TrkB, p-TrkB, AKT, p-AKT, ERK, and p-ERK in the hippocampus of rats was detected by Western blotting. The results showed that ω-3PUFAs attenuated MK-801-induced cognitive impairment and hippocampal neurons loss, reversed the injury of the CREB/BDNF/TrkB pathway induced by MK-801, and antagonized MK-801-induced down-regulation of p-AKT and p-ERK in the hippocampus of rats. In conclusion, ω-3PUFAs enhances the CREB/BDNF/TrkB pathway by activating ERK and AKT, thereby increasing the synaptic plasticity and decreasing neuron loss, and antagonizing MK-801-induced cognitive impairment in schizophrenic rats.

The effect of Anshen Dingzhi Fang on tau protein phosphorylation and DNF/TrkB signaling pathway in Alzheimer's disease rats

Objective:To observe the effect of Anshen Dingzhi Decoction on tau phosphorylation in hippocampus of Alzheimer's disease rat model and its related mechanism.Methods:SD rats were randomly divided into control group,model group,Anshen Dingzhi Decoction(low,medium and high dose group)and Dopazide group.Except for the control group,the rats in the other groups were injected with streptozotocin into the lateral ventricle to replicate the model of Alzheimer's disease and then given corresponding drugs for 2 weeks.orris water maze test was used to detect learning and memory ability of rats,HE staining was used to detect hippocampal histological morphology,Western-blot was used to detect tau phosphorylation level and expression abundance of BDNF and TrkB protein in hippocampal tissue of rats.Results:The escape latency of the model group was significantly increased,the number of crossing platforms and effective residence time were significantly reduced,the phosphorylation level of tau protein was significantly increased,and the phosphorylation levels of BDNF and TrkB protein were significantly decreased when compared with the control group,the difference has statistically significant(P<0.05).Anshen Dingzhi Fang could significantly reduce the escape latency of AD rats,increase the number of crossing platforms and effective residence time,inhibit the phosphorylation of tau protein,and up-regulate the phosphorylation of BDNF and TrkB protein,the difference was statistically significant when compared with the model group(P<0.05).Conclusion:Anshen Dingzhi Fang can inhibit the phosphorylation of tau protein by activating BDNF/TrkB signaling pathway and promote the learning and memory ability of AD rats.

The biochemical pathways of central nervous system neural degeneration in niacin deficiency

Neural degeneration is a very complicated process. In spite of all the advancements in the molecular chemistry, there are many unknown aspects of the phenomena of neurodegeneration which need to be put together. It is a common sequela of the conditions of niacin deficiency. Neural degeneration in Pellagra manifests as chromatolysis mainly in pyramidal followed by other neurons and glial cells. However, there is a gross lack of understanding of biochemi- cal mechanisms of neurodegeneration in niacin deficiency states. Because of the necessity of niacin or its amide derivative NAD in a number of biochemical pathways, it is understandable that several of these pathways may be involved in the common outcome of neural degener- ation. Here, we highlight five pathways that could be involved in the neuraldegeneration for which evidence has accumulated through several studies. These pathways are： 1） the trypto- phan-kyneurenic acid pathway, 2） the mitochondrial ATP generation related pathways, 3） the poly （ADP-ibose） polymerase （PARP） pathway, 4） the BDNF-TRKB Axis abnormalities, 5） the genetic influences of niacin deficiency.

Antidepressant effect of electroacupuncture regulates signal targeting in the brain and increases brain- derived neurotrophic factor levels

Electroacupuncture improves depressive behavior faster and with fewer adverse effects than antidepressant medication. However, the antidepressant mechanism of electroacupuncture remains poorly understood. Here, we established a rat model of chronic unpredicted mild stress, and then treated these rats with electroacupuncture at Yintang （EX-HN3） and Baihui （DU20） with sparse waves at 2 Hz and 0.6 mA for 30 minutes, once a day. We found increased horizontal and vertical activity, and decreased immobility time, at 2 and 4 weeks after treatment. Moreover, levels of neurotransmitters （5-hydroxytryptamine, glutamate, and y-aminobutyric acid） and protein levels of brain-derived neurotrophic factor and brain-derived neurotrophic factor-related proteins （TrkB, protein kinase A, and phosphorylation of cyclic adenosine monophosphate response element binding protein） were increased in the hippocampus. Similarly, protein kinase A and TrkB mRNA levels were increased, and calcium-calmodulin-dependent protein kinase lI levels decreased. These findings suggest that electroacupuncture increases phosphorylation of cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor levels by regulating multiple targets in the cyclic adenosine rnonophosphate response element binding protein signal- ing pathway, thereby promoting nerve regeneration, and exerting an antidepressive effect.

Porcine placental peptides improve neuroblast proliferation and differentiation via enhancement of TrkB and BDNF levels in D-glatacose-induced mouse aging model

Aging affects the nervous system as well as other organs.In our study,we aimed to study the pharmacological effects and mechanism of porcine placental peptides(PPP)in aging process,and to observe the changes of neuroblast proliferation and differentiation as well as partial gene expression in hippocampus of D-galactose-induced aged mouse.Based on the analysis of experimental results,it was confirmed that PPP significantly improved neurobalst proliferation and differentiation in the mouse hippocampal DG by ki-67 and DCX immunohistochemistry.This result showed that PPP had anti-aging effects on D-galactoseinduced aging mouse model.Moreover,we observed up-regulated expressions of BDNF and TrkB proteins and down-regulated expressions of Caspase 3,8,and 9 proteins in the PPP-treated mouse hippocampus.Therefore,our results showed that PPP obviously improved neuroblast proliferation and differentiation,and its anti-aging effect might berelated to down-regulation of apoptosis-related proteins,including Caspase 3,8,and 9,via BDNF/TrkB pathway.Our findings provided valuable evidence for its applications in the health and medicine sectors.