Telomerase increasing compound protects hippocampal neurons from amyloid beta toxicity by enhancing the expression of neurotrophins and plasticity related genes

AbstractThe telomerase reverse transcriptase protein, TERT, is expressed in the adult brain and its exogenic expression protects neurons from oxidative stress and from the cytotoxicity of amyloid beta (Aβ). We previously showed that telomerase increasing compounds (AGS) protected neurons from oxidative stress. Therefore, we suggest that increasing TERT by AGS may protect neurons from the Aβ-induced neurotoxicity by influencing genes and factors that participate in neuronal survival and plasticity. Here we used a primary hippocampal cell culture exposed to aggregated Aβ and hippocampi from adult mice. AGS treatment transiently increased TERT gene expression in hippocampal primary cell cultures in the presence or absence of Aβ and protected neurons from Aβ induced neuronal degradation. An increase in the expression of Growth associated protein 43 (GAP43), and Feminizing locus on X-3 genes (NeuN), in the presence or absence of Aβ, and Synaptophysin (SYP) in the presence of Aβ was observed. GAP43, NeuN, SYP, Neurotrophic factors (NGF, BDNF), beta-catenin and cyclin-D1 expression were increased in the hippocampus of AGS treated mice. This data suggests that increasing TERT by pharmaceutical compounds partially exerts its neuroprotective effect by enhancing the expression of neurotrophic factors and neuronal plasticity genes in a mechanism that involved Wnt/beta-catenin pathway.

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Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice

Molecular Neurobiology ◽

10.1007/s12035-016-9795-4 ◽

2016 ◽

Vol 54 (3) ◽

pp. 2269-2285 ◽

Cited By ~ 61

Author(s):

Ashfaq Ahmad ◽

Tahir Ali ◽

Hyun Young Park ◽

Haroon Badshah ◽

Shafiq Ur Rehman ◽

...

Keyword(s):

Amyloid Beta ◽

Neuroprotective Effect ◽

Synaptic Dysfunction ◽

Adult Mice

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Dexmedetomidine Alleviates Hypoxia-Induced Synaptic Loss and Cognitive Impairment via Inhibition of Microglial NOX2 Activation in the Hippocampus of Neonatal Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6643171 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Xiaohui Chen ◽

Dongtai Chen ◽

Qiang Li ◽

Shuyan Wu ◽

Jiahao Pan ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Impairment ◽

Hippocampal Neurons ◽

Neuronal Damage ◽

Neuroprotective Effect ◽

Neurological Deficits ◽

Neonatal Rats ◽

Synaptic Loss ◽

Neonatal Hypoxia ◽

Bv2 Microglia

Background. Perinatal hypoxia is a universal cause of death and neurological deficits in neonates worldwide. Activation of microglial NADPH oxidase 2 (NOX2) leads to oxidative stress and neuroinflammation, which may contribute to hypoxic damage in the developing brain. Dexmedetomidine has been reported to exert potent neuroprotection in several neurological diseases, but the mechanism remains unclear. We investigated whether dexmedetomidine acts through microglial NOX2 to reduce neonatal hypoxic brain damage. Methods. The potential role of microglial NOX2 in dexmedetomidine-mediated alleviation of hypoxic damage was evaluated in cultured BV2 microglia and neonatal rats subjected to hypoxia. In vivo, neonatal rats received dexmedetomidine (25 μg/kg, i.p.) 30 min before or immediately after hypoxia (5% O2, 2 h). Apocynin-mediated NOX inhibition and lentivirus-mediated NOX2 overexpression were applied to further assess the involvement of microglial NOX2 activation. Results. Pre- or posttreatment with dexmedetomidine alleviated hypoxia-induced cognitive impairment, restored damaged synapses, and increased postsynaptic density-95 and synaptophysin protein expression following neonatal hypoxia. Importantly, dexmedetomidine treatment suppressed hypoxia-induced microglial NOX2 activation and subsequent oxidative stress and the neuroinflammatory response, as reflected by reduced 4-hydroxynonenal and ROS accumulation, and decreased nuclear NF-κB p65 and proinflammatory cytokine levels in cultured BV2 microglia and the developing hippocampus. In addition, treating primary hippocampal neurons with conditioned medium (CM) from hypoxia-activated BV2 microglia resulted in neuronal damage, which was alleviated by CM from dexmedetomidine-treated microglia. Moreover, the neuroprotective effect of dexmedetomidine was reversed in NOX2-overexpressing BV2 microglia and diminished in apocynin-pretreated neonatal rats. Conclusion. Dexmedetomidine targets microglial NOX2 to reduce oxidative stress and neuroinflammation and subsequently protects against hippocampal synaptic loss following neonatal hypoxia.

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Current Pathogenesis of Alzheimer’s Disease and Plants Derived Neuroprotective Phytoconstituents: A Comprehensive Review

Current Psychopharmacologye ◽

10.2174/2211556010666210728123937 ◽

2021 ◽

Vol 10 ◽

Author(s):

Anil Kumar Pradhan ◽

Bimala Tripathy ◽

Bimalendu Chowdhury ◽

Sasmita Kumari Acharjya ◽

Rajaram Das

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Neurodegenerative Disorders ◽

Neuroprotective Effect ◽

Vital Role ◽

Bioactive Constituents ◽

Different Types

Background: The exact pathogenesis of Alzheimer’s disease is still a matter to debate, currently there is no reliable therapy established for Alzheimer’s disease. However, several pieces of evidence suggest that the use of plant based phytoconstituents mainly delays the onset of Alzheimer. So, in this review, we collect information about the cause of Alzheimer’s disease hypothesis and neuroprotective effect of phytoconstituents. Objective: This review paper aimed to analyze the current pathogenesis of Alzheimer’s disease and the therapeutic effect of plant phytoconstituents that play a vital role in neuroprotective and antistress activities in Alzheimer’s disease and other neurodegenerative disorders. Methods: The source of literature review obtained from Scopus, Science direct, PubMed, web of science database, and journal by using Alzheimer’s pathogenesis, neuroinflammation, oxidative stress, amyloid beta, flavonoids, alkaloids are important part of these review research. Results: The current review explored the different types of pathogenesis involved in Alzheimer’s disease and the role of phytoconstituents in treatment of it. The collected information showed that plant based constituents inhibit the major cause of Alzheimer’s disease related to amyloid beta, tau protein, oxidative stress, neuroinflammation etc. Conclusion: The study provide the clue for the investigation of eminent bioactive constituents may serves as an alternative candidate against Alzheimer’s disease and other neurodegenerative disorders.

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Neuroprotective Effect of ent-Kaur-15-en-17-al-18-oic Acid on Amyloid Beta Peptide-Induced Oxidative Apoptosis in Alzheimer’s Disease

Molecules ◽

10.3390/molecules25010142 ◽

2019 ◽

Vol 25 (1) ◽

pp. 142 ◽

Cited By ~ 2

Author(s):

Caiyun Zhang ◽

Xingming Zhao ◽

Shiqi Lin ◽

Fangyuan Liu ◽

Jiahui Ma ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Beta ◽

Neuroprotective Effect ◽

B Cell Lymphoma ◽

Nuclear Factor Κb ◽

Amyloid Beta Peptide ◽

Nuclear Factor ◽

Beta Peptide

ent-Kaur-15-en-17-al-18-oic acid, extracted from the Chinese well known folk herb Leontopodium longifolium, performed a significantly neuroprotective effect on amyloid beta peptide 25-35 (Aβ25-35)-induced SH-SY5Y cells neurotoxicity in Alzheimer’s disease. The results demonstrated that this compound maintained oxidative stress balance, reduced levels of reactive oxygen species (ROS), malondialdehyde (MDA), and improved contents of glutathione (GSH) and superoxide dismutase (SOD) without obvious cytotoxicity. This compound also obviously relieved oxidative stress-induced apoptosis associated with p53 and nuclear factor κB (NF-κB) pathways accompanied by upregulating B-cell lymphoma-2 (bcl-2) and downregulating p53, nuclear factor κB (NF-κB), Bax, Cleaved-caspase 3, and Cytochrome C protein expressions further. Briefly, ent-kaur-15-en-17-al-18-oic acid protected cells from oxidative apoptosis associated with p53 and NF-κB pathways.

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Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons

Neural Plasticity ◽

10.1155/2016/4145708 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 14

Author(s):

Bianca Seifert ◽

Robert Eckenstaler ◽

Raik Rönicke ◽

Julia Leschik ◽

Beat Lutz ◽

...

Keyword(s):

Amyloid Beta ◽

Hippocampal Neurons ◽

Early Time ◽

Retrograde Transport ◽

Secretory Protein ◽

Adult Brain ◽

Model Systems ◽

Extracellular Medium ◽

Transgenic Expression ◽

Brain Functions

The neurotrophin brain derived neurotrophic factor (BDNF) is an important growth factor in the CNS. Deficits in transport of this secretory protein could underlie neurodegenerative diseases. Investigation of disease-related changes in BDNF transport might provide insights into the cellular mechanism underlying, for example, Alzheimer’s disease (AD). To analyze the role of BDNF transport in AD, live cell imaging of fluorescently labeled BDNF was performed in hippocampal neurons of different AD model systems. BDNF and APP colocalized with low incidence in vesicular structures. Anterograde as well as retrograde transport of BDNF vesicles was reduced and these effects were mediated by factors released from hippocampal neurons into the extracellular medium. Transport of BDNF was altered at a very early time point after onset of human APP expression or after acute amyloid-beta(1-42) treatment, while the activity-dependent release of BDNF remained unaffected. Taken together, extracellular cleavage products of APP induced rapid changes in anterograde and retrograde transport of BDNF-containing vesicles while release of BDNF was unaffected by transgenic expression of mutated APP. These early transport deficits might lead to permanently impaired brain functions in the adult brain.

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Rabies Virus Infection of Primary Neuronal Cultures and Adult Mice: Failure To Demonstrate Evidence of Excitotoxicity

Journal of Virology ◽

10.1128/jvi.01272-06 ◽

2006 ◽

Vol 80 (20) ◽

pp. 10270-10273 ◽

Cited By ~ 39

Author(s):

Simon C. Weli ◽

Courtney A. Scott ◽

Christopher A. Ward ◽

Alan C. Jackson

Keyword(s):

Virus Infection ◽

Rabies Virus ◽

Hippocampal Neurons ◽

Neuroprotective Effect ◽

Neuronal Cultures ◽

Primary Neuronal Cultures ◽

Trypan Blue Exclusion ◽

Beneficial Effects ◽

Adult Mice ◽

Rabies Virus Infection

ABSTRACT Cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the CVS strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. The NMDA (N-methyl-d-aspartate acid) antagonists ketamine (125 μM) and MK-801 (60 μM) were found to have no significant neuroprotective effect on CVS-infected neurons, while the caspase inhibitor Ac-Asp-Glu-Val aspartic acid aldehyde (25 μM) exerted a marked neuroprotective effect. Glutamate-stimulated increases in levels of intracellular calcium were reduced in CVS-infected hippocampal neurons. Ketamine (120 mg/kg of body weight/day intraperitoneally) given to CVS-infected adult mice produced no beneficial effects. We have found no supportive evidence that excitotoxicity plays an important role in rabies virus infection.

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Tilapia Head Protein Hydrolysate Attenuates Scopolamine-Induced Cognitive Impairment through the Gut-Brain Axis in Mice

Foods ◽

10.3390/foods10123129 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3129

Author(s):

Jun Ji ◽

Xiangzhou Yi ◽

Yujie Zhu ◽

Hui Yu ◽

Shuqi Huang ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Impairment ◽

Cholinergic System ◽

Hippocampal Neurons ◽

Dietary Intervention ◽

Protein Hydrolysate ◽

Neuroprotective Effect ◽

Stress System ◽

Innovative Strategy ◽

Head Protein

The destruction of the homeostasis in the gut-brain axis can lead to cognitive impairment and memory decline. Dietary intervention with bioactive peptides from aquatic products is an innovative strategy to prevent cognitive deficits. The present study aimed to determine the neuroprotective effect of tilapia head protein hydrolysate (THPH) on scopolamine-induced cognitive impairment in mice, and to further explore its mechanism through the microbiota–gut-brain axis. The results showed that THPH administration significantly improved the cognitive behavior of mice, and normalized the cholinergic system and oxidative stress system of the mice brain. The histopathological observation showed that THPH administration significantly reduced the pathological damage of hippocampal neurons, increased the number of mature neurons marked by NeuN and delayed the activation of astrocytes in the hippocampus of mice. In addition, THPH administration maintained the stability of cholinergic system, alleviated oxidative stress and further improved the cognitive impairment by reshaping the gut microbiota structure of scopolamine-induced mice and alleviating the disorder of lipid metabolism and amino acid metabolism in serum. In conclusion, our research shows that THPH supplementation is a nutritional strategy to alleviate cognitive impairment through the gut-brain axis.

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