The influence of GAPT extraction on synapse loss of APPswe/PS1dE9 transgenic mice via adjusting Bcl‐2/Bax balance

Shi, Jing; Zhang, Xuekai; Ni, Jingnian; Wei, Mingqing; Li, Ting; Zhou, Bingling; Li, Zheng; Zhang, Liping; Wang, Pengwen; Tian, Jinzhou; Wang, Yongyan

doi:10.1016/j.trci.2018.10.008

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…Thus, we next determined the effect of serum on the presynaptic marker synaptophysin and AMPA receptor GluA1. Consistent with previous studies [ 53 , 54 ], the 8–9-month-old APP/PS1 male mouse model showed a significant decrease in synaptophysin and GluA1 expression in the DG and CA3, but not in CA1 of the hippocampus, compared to observations in the age-matched WT controls (Fig. 7A–E ; for synaptophysin, decreases of 32.6% and 47.8% in the DG and CA3, respectively; decreases of 42.5% in CA3 for GluA1).…”

Section: Resultssupporting

confidence: 94%

VEGF-A in serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration

Qi,

Zuo,

et al. 2023

Mol Psychiatry

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Activation of innate immunity in the brain is a prominent feature of Alzheimer’s disease (AD). The present study investigated the regulation of innate immunity by wild-type serum injection in a transgenic AD mouse model. We found that treatment with wild-type mouse serum significantly reduced the number of neutrophils and microglial reactivity in the brains of APP/PS1 mice. Mimicking this effect, neutrophil depletion via Ly6G neutralizing antibodies resulted in improvements in AD brain functions. Serum proteomic analysis identified vascular endothelial growth factor-A (VEGF-A) and chemokine (C-X-C motif) ligand 1 (CXCL1) as factors enriched in serum samples, which are crucial for neutrophil migration and chemotaxis, leukocyte migration, and cell chemotaxis. Exogenous VEGF-A reversed amyloid β (Aβ)-induced decreases in cyclin-dependent kinase 5 (Cdk5) and increases in CXCL1 in vitro and blocked neutrophil infiltration into the AD brain. Endothelial Cdk5 overexpression conferred an inhibitory effect on CXCL1 and neutrophil infiltration, thereby restoring memory abilities in APP/PS1 mice. Our findings uncover a previously unknown link between blood-derived VEGF signaling and neutrophil infiltration and support targeting endothelial Cdk5 signaling as a potential therapeutic strategy for AD.

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Section: Resultssupporting

confidence: 94%

VEGF-A in serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration

Qi,

Zuo,

et al. 2023

Mol Psychiatry

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show abstract

“…Thus, we determined the effect of young serum on the presynaptic marker synaptophysin and AMPA receptor GluA1. Consistent with previous studies 43,44 , the 8-to 9-month-old APP/PS1 male mouse model showed a signi cant decrease in synaptophysin and GluA1 expression in the dentate gyrus (DG) and CA3, but not in CA1 of the hippocampus, compared to observations in the age-matched WT controls (Fig. 7A-E; decreases of 32.6% and 47.8% in the DG and CA3, respectively).…”

Section: Endothelial Cdk5 Overexpression Mitigates Neutrophil In Ltra...supporting

confidence: 91%

Young serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration

Ke¹,

Zuo

et al. 2022

Preprint

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Activation of innate immunity in the brain is a prominent feature of Alzheimer's disease (AD). The present study investigated the regulation of innate immunity by young serum in a transgenic AD mouse model. We found that young serum significantly reduced the number of neutrophils and microglial reactivity in the brains of APP/PS1 mice. Neutrophil depletion via Ly6G neutralizing antibodies mimicked the benefits of young serum on AD brain functions. Serum proteomic analysis of young serum revealed significant enrichment of the factors VEGF-A and CXCL1, which are crucial for neutrophil migration and chemotaxis, leukocyte migration, and cell chemotaxis. Intravenously injected VEGF-A reversed Aβ-induced decreases in Cdk5 and increases in CXCL1 in vitro and blocked neutrophil infiltration into the AD brain. Endothelial Cdk5 overexpression conferred an inhibitory effect on CXCL1 and neutrophil infiltration and thereby restored memory in APP/PS1 mice. Our data uncover a previously unknown link between blood-derived VEGF signaling and neutrophil infiltration and provide a rationale for targeting endothelial Cdk5 signaling as a potential therapeutic strategy for AD.

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“…GAPT can increase APP/PS1 transgenic mice's brain glucose uptake and glucose transport and improve the insulin signaling pathway (Mana et al, 2019). Moreover, synapse damage ameliorated by GAPT via regulating bcl‐2/Bax balance (Shi et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine

et al. 2020

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Background Cholinergic dysfunction and oxidative stress are the crucial mechanisms of Alzheimer's disease (AD). GAPT, also called GEPT (a combination of several active components extracted from the Chinese herbs ginseng, epimedium, polygala and tuber curcumae) or Jinsiwei, is a patented Chinese herbal compound, has been clinically widely used to improve learning and memory impairment, but whether it can play a neuroprotective role by protecting cholinergic neurons and reducing oxidative stress injury remains unclear. Methods Male ICR mice were intraperitoneally injected with scopolamine (3 mg/kg) to establish a learning and memory disordered model. An LC‐MS method was established to study the chemical compounds and in vivo metabolites of GAPT. After scopolamine injection, a step‐down passive‐avoidance test (SDPA) and a Y maze test were used to estimate learning ability and cognitive function. In addition, ELISA detected the enzymatic activities of acetylcholinesterase (AChE), acetylcholine (ACh), choline acetyltransferase (ChAT), malondialdehyde (MDA), glutathione peroxidase (GPX), and total superoxide dismutase (T‐SOD). The protein expressions of AChE, ChAT, SOD1, and GPX1 were observed by western blot, and the distribution of ChAT, SOD1, and GPX1 was observed by immunohistochemical staining. Results After one‐half or 1 month of intragastric administration, GAPT can ameliorate scopolamine‐induced behavioral changes in learning and memory impaired mice. It can also decrease the activity of MDA and protein expression level of AChE, increase the activity of Ach, and increase activity and protein expression level of ChAT, SOD, and GPX in scopolamine‐treated mice. After one and a half month of intragastric administration of GAPT, echinacoside, salvianolic acid A, ginsenoside Rb1, ginsenoside Rg2, pachymic acid, and beta asarone could be absorbed into mice blood and pass through BBB. Conclusions GAPT can improve the learning and memory ability of scopolamine‐induced mice, and its mechanism may be related to protecting cholinergic neurons and reducing oxidative stress injury.

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The influence of GAPT extraction on synapse loss of APPswe/PS1dE9 transgenic mice via adjusting Bcl‐2/Bax balance

Cited by 7 publications

References 41 publications

VEGF-A in serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration

VEGF-A in serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration

Young serum protects against memory impairment in APP/PS1 transgenic mice by blocking neutrophil infiltration

GAPT regulates cholinergic dysfunction and oxidative stress in the brains of learning and memory impairment mice induced by scopolamine

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