Vascular endothelial growth factor improves the cognitive decline of Alzheimer’s disease via concurrently inducing the expression of ADAM10 and reducing the expression of β-site APP cleaving enzyme 1 in Tg2576 mice

Guo, H. W.; Xia, Deyu; Liao, Shaohua; Niu, Bing; Tang, Jigang; Hu, Huaiqiang; Qian, Hongyan; Cao, Bingzhen

doi:10.1016/j.neures.2018.04.003

Cited by 16 publications

(13 citation statements)

References 29 publications

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“…Growth factors (VEGF and its receptors, FGF, EGF, HB-EGF) are major players in vasculogenesis and neuronal function [54]. Low levels of plasma EGF and VEGF have also been revealed in AD in prior studies [55,56]. The present study demonstrates a decrease in EV content of GFs )UPAR, VEGF-D,VEGFR-2 and 3, FGF-4, EGF, and ANG-1), which could contribute to the vascular and neuronal damage observed in moderate AD.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles of Alzheimer’s Disease Patients as a Biomarker for Disease Progression

et al. 2020

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Alzheimer's disease (AD) is a progressive neurodegenerative brain pathology and the most common form of dementia. Evidence suggests that extracellular vesicles (EVs) containing cytokines and microRNA are involved in inflammation regulation. The current study aimed to explore a potential impact of AD patients' EVs on disease progression. Blood samples were collected after obtaining signed informed consent (No. 0462-14-RMB) from 42 AD patients at three stages of disease severity and from 19 healthy controls (HC). EV size and concentration were studied by nanotracking analysis. EV membrane antigens were defined by flow cytometry and Western blot; EV protein contents were screened by protein array; the miRNA content was screened by nanostring technology and validated by RT-PCR. HC and AD patients' EVs consisted of a mixture of small (< 100 nm) and larger vesicles. The myelin oligodendrocyte glycoprotein (MOG) expression on EVs correlated with disease severity. EVs of patients with moderate and severe AD had significantly higher levels of MOG, compared with mild AD patients. Levels of EVs expressing the axonal glycoprotein CD171 were significantly higher in severe AD patients than in HC. Increase in endothelial EVs was observed in AD patients. An above twofold increase was found in the content of inflammatory cytokines and > 50% decrease in growth factors in AD patients' EVs compared with HC-EVs. Levels of let-7g-5p, miR126-3p, miR142-3p, miR-146a-5p, and mir223-3p correlated with disease severity. Neural damage, specific miRNA downregulation, and inflammatory cytokine upregulation, found in patients' EVs, might be used as a biomarker reflecting AD severity.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles of Alzheimer’s Disease Patients as a Biomarker for Disease Progression

et al. 2020

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“…Interestingly, it has also been proven to be neuroprotective. Numerous works have demonstrated its trophic effects after different types of neuronal lesions (Pan et al, 2013;Beecher et al, 2018;Calvo et al, 2018;Zeng et al, 2018;Chi et al, 2019), excitotoxic injury (Matsuzaki et al, 2001;Tovar-y-Romo et al, 2007;Tovary-Romo and Tapia, 2010), ischemia (Sun et al, 2003;Guo et al, 2016;Geiseler and Morland, 2018;Wang et al, 2018), epilepsy (Nicoletti et al, 2008(Nicoletti et al, , 2010, and neurologic diseases such as motoneuronal degeneration in amyotrophic lateral sclerosis (ALS) and spinal-bulbar muscular atrophy (Kennedýs disease), peripheral neuropathies, Alzheimer¨s disease, Parkinson¨s disease, demyelinating diseases, and also in traumatic spinal injury (enhancing nerve repair) and in neovascular ocular diseases (Storkebaum et al, 2005;Zachary, 2005;Wang et al, 2007Wang et al, , 2016Lange et al, 2016;Guo et al, 2019). Although VEGF can act on different neuronal types (Storkebaum et al, 2004;Cabezas et al, 2019), a clear link has been established between VEGF and motoneurons (Lladó et al, 2013), mainly due to the appearance of symptoms resembling ALS when the levels of VEGF are low, as is the case for the VEGF d /d mutant mice.…”

Section: Introductionmentioning

confidence: 99%

A Single Intraventricular Injection of VEGF Leads to Long-Term Neurotrophic Effects in Axotomized Motoneurons

Calvo

Cruz

Pastor

2020

eNeuro

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Vascular endothelial growth factor (VEGF) has been recently demonstrated to induce neuroprotective and synaptotrophic effects on lesioned neurons. Hitherto, the administration of VEGF in different animal models of lesion or disease has been conducted following a chronic protocol of administration. We questioned whether a single dose of VEGF, administered intraventricularly, could induce long-term neurotrophic effects on injured motoneurons. For this purpose, we performed in cats the axotomy of abducens motoneurons and the injection of VEGF into the fourth ventricle in the same surgical session and investigated the discharge characteristics of axotomized and treated motoneurons by single-unit extracellular recordings in the chronic alert preparation. We found that injured motoneurons treated with a single VEGF application discharged with normal characteristics, showing neuronal eye position (EP) and velocity sensitivities similar to control, thereby preventing the axotomy-induced alterations. These effects were present for a prolonged period of time (50 d) after VEGF administration. By confocal immunofluorescence we also showed that the synaptic stripping that ensues lesion was not present, rather motoneurons showed a normal synaptic coverage. Moreover, we demonstrated that VEGF did not lead to any angiogenic response pointing to a direct action of the factor on neurons. In summary, a single dose of VEFG administered just after motoneuron axotomy is able to prevent for a long time the axotomy-induced firing and synaptic alterations without any associated vascular sprouting. We consider that these data are of great relevance due to the potentiality of VEGF as a therapeutic agent in neuronal lesions and diseases.

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“…Vascular endothelial growth factor (VEGF) is well-known for its vasculogenic and angiogenic activity ( 1 – 3 ). In addition, this molecule also has powerful neuroprotective effects after different types of insult in the CNS, such as mechanical lesions ( 4 – 7 ), excitotoxic injury ( 8 ), oxidative stress ( 9 ), ischemia ( 10 , 11 ), epilepsy ( 12 , 13 ), and neurological diseases ( 14 – 16 ).…”

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confidence: 99%

VEGF is an essential retrograde trophic factor for motoneurons

Calvo

Hernández

Cruz

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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VEGF was initially discovered due to its angiogenic activity and therefore named “vascular endothelial growth factor.” However, its more recently discovered neurotrophic activity may be evolutionarily more ancient. Our previous work showed that all the changes produced by axotomy on the firing activity and synaptic inputs of abducens motoneurons were completely restored after VEGF administration. Therefore, we hypothesized that the lack of VEGF delivered by retrograde transport from the periphery should also affect the physiology of otherwise intact abducens motoneurons. For VEGF retrograde blockade, we chronically applied a neutralizing VEGF antibody to the lateral rectus muscle. Recordings of extracellular single-unit activity and eye movements were made in alert cats before and after the application of the neutralizing antibody. Our data revealed that intact, noninjured abducens motoneurons retrogradely deprived of VEGF exhibited noticeable changes in their firing pattern. There is a general decrease in firing rate and a significant reduction in eye position and eye velocity sensitivity (i.e., a decrease in the tonic and phasic components of their discharge, respectively). Moreover, by means of confocal immunocytochemistry, motoneurons under VEGF blockade showed a marked reduction in the density of afferent synaptic terminals contacting with their cell bodies. Altogether, the present findings demonstrate that the lack of retrogradely delivered VEGF renders abducens motoneurons into an axotomy-like state. This indicates that VEGF is an essential retrograde factor for motoneuronal synaptic drive and discharge activity.

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Vascular endothelial growth factor improves the cognitive decline of Alzheimer’s disease via concurrently inducing the expression of ADAM10 and reducing the expression of β-site APP cleaving enzyme 1 in Tg2576 mice

Cited by 16 publications

References 29 publications

Extracellular Vesicles of Alzheimer’s Disease Patients as a Biomarker for Disease Progression

Extracellular Vesicles of Alzheimer’s Disease Patients as a Biomarker for Disease Progression

A Single Intraventricular Injection of VEGF Leads to Long-Term Neurotrophic Effects in Axotomized Motoneurons

VEGF is an essential retrograde trophic factor for motoneurons

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