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

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.

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

Foods ◽  
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.

CREB Protects against Temporal Lobe Epilepsy Associated with Cognitive Impairment by Controlling Oxidative Neuronal Damage

2019 ◽  
Vol 19 (5-6) ◽  
pp. 225-237 ◽  
Author(s):  
Jihong Xing ◽  
Dongfeng Han ◽  
Dahai Xu ◽  
Xingliang Li ◽  
Lichao Sun
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Temporal Lobe Epilepsy ◽  
Cognitive Dysfunction ◽  
Neuronal Apoptosis ◽  
Neuronal Damage ◽  
Primary Neurons ◽  
Mitochondrial Oxidative Stress ◽  
Memory Decline ◽  
Downstream Signaling

Background: Cognitive dysfunction as a common comorbidity of epilepsy often manifests as learning and memory impairments in patients with temporal lobe epilepsy (TLE). The pathogenetic molecular mechanisms underlying epilepsy-associated cognitive dysfunction are incompletely understood. We investigated the role of cAMP response element binding protein (CREB) and its downstream signaling pathways in the pathogenesis of cognitive impairment in mice with TLE. Methods: Plasmid vectors of CREB-specific short-hairpin RNAs and CREB cDNA were prepared and transfected into primary neurons. Neuronal apoptosis and mitochondrial oxidative stress were assessed by flow cytometry. For in vivo studies, TLE in mice was induced by pilocarpine injection, and TLE-associated memory decline was evaluated using the Morris water maze after treatment with the CREB inhibitor 666-15, with or without the mitochondria-specific antioxidant MitoQ. CREB and its downstream mediators were examined by Western blotting analysis and quantitative reverse transcription polymerase chain reaction. Results: CREB knockdown induced mitochondrial reactive oxygen species production and apoptosis in primary neurons whereas CREB overexpression brought the opposite effects. The TLE mice exhibited elevated oxidative stress and neuronal apoptosis with decreased expression of CREB and its downstream mediators including PKA, CaMKIV, arc, and c-fos. CREB inhibition exacerbated TLE-associated oxidative neuronal apoptosis and memory decline. MitoQ treatment restored the expression of CREB and its downstream mediators, and prevented TLE-associated oxidative neuronal damage and memory deficits aggravated by CREB inhibition. Conclusion: CREB plays a significant role in TLE-associated oxidative neuronal damage and memory impairment. This novel finding provides the evidence of the relationship between CREB and mitochondrial oxidative stress and cognitive dysfunction in epilepsy. Mitochondria-specific antioxidants such as MitoQ may alleviate TLE-associated cognitive dysfunction through activation of CREB and its downstream signaling pathways.

scholarly journals Neuroprotective Effect of Antioxidants in the Brain

2020 ◽  
Vol 21 (19) ◽  
pp. 7152 ◽  
Author(s):  
Kyung Hee Lee ◽  
Myeounghoon Cha ◽  
Bae Hwan Lee
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Intracellular Signaling ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
High Energy ◽  
Antioxidant Compounds ◽  
The Brain

The brain is vulnerable to excessive oxidative insults because of its abundant lipid content, high energy requirements, and weak antioxidant capacity. Reactive oxygen species (ROS) increase susceptibility to neuronal damage and functional deficits, via oxidative changes in the brain in neurodegenerative diseases. Overabundance and abnormal levels of ROS and/or overload of metals are regulated by cellular defense mechanisms, intracellular signaling, and physiological functions of antioxidants in the brain. Single and/or complex antioxidant compounds targeting oxidative stress, redox metals, and neuronal cell death have been evaluated in multiple preclinical and clinical trials as a complementary therapeutic strategy for combating oxidative stress associated with neurodegenerative diseases. Herein, we present a general analysis and overview of various antioxidants and suggest potential courses of antioxidant treatments for the neuroprotection of the brain from oxidative injury. This review focuses on enzymatic and non-enzymatic antioxidant mechanisms in the brain and examines the relative advantages and methodological concerns when assessing antioxidant compounds for the treatment of neurodegenerative disorders.

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

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Natalie Baruch-Eliyahu ◽  
Vladislav Rud ◽  
Alex Braiman ◽  
Esther Priel
Keyword(s):  
Oxidative Stress ◽  
Amyloid Beta ◽  
Neurotrophic Factors ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Adult Brain ◽  
Beta Catenin ◽  
Adult Mice ◽  
Hippocampal Cell Culture ◽  
Neuronal Degradation

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.

Neuroprotective effect of Chunghyuldan from amyloid beta oligomer induced neuroinflammation in vitro and in vivo

2014 ◽  
Vol 92 (6) ◽  
pp. 429-437 ◽  
Author(s):  
Hyo Geun Kim ◽  
Ji-Young Kim ◽  
Wei-Wan Whang ◽  
Myung Sook Oh
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Beta ◽  
Antioxidant Activities ◽  
Neuronal Damage ◽  
Biological Effects ◽  
Neuroprotective Effect ◽  
In Vivo Models ◽  
Aβ Oligomer

Microglia-mediated inflammation is a major pathological mechanism contributing to Alzheimer’s disease (AD), and has been proposed as a potential therapeutic target. Chunghyuldan (CHD; Qingxue-dan in Chinese and Daio-Orengedokuto in Japanese) possesses wide-ranging biological effects, including anti-hyperlipidemic, anti-stroke, anti-inflammatory, and antioxidant activities that could affect neurological functions. In this study, we examined the effects of CHD in in-vitro and in-vivo models of AD induced by the oligomeric form of amyloid-beta (Aβ oligomer), which acts directly on microglia-mediated neuroinflammation to result in neuronal damage and cognitive impairment. CHD at 0.1–100 μg·mL−1 significantly protected PC12 cells and rat primary hippocampal cells from Aβ oligomer1–42 toxicity. In addition, CHD at 1–10 μg·mL−1 inhibited Aβ oligomer1–42 induced production of nitric oxide, tumor necrosis factor-α, and interleukin-1β in microglial cells. In an in-vivo AD model, administration of CHD (50 mg·(kg body mass)−1, for 5 days, per oral) inhibited the activation of astrocytes and microglia in the dentate gyrus and neuronal damage in the CA1 of the ipsilateral hippocampus. Moreover, CHD ameliorated cognitive impairment induced by Aβ oligomer1–42 toxicity. These results demonstrate the neuroprotective effects of CHD through inhibition of microglia-mediated neuroinflammation in in-vitro and in-vivo AD-like models induced by Aβ oligomer1–42 toxicity.

scholarly journals The neuroprotective effect of Riparin IV on oxidative stress and neuroinflammation related to chronic stress-induced cognitive impairment

2020 ◽  
Vol 122 ◽  
pp. 104758
Author(s):  
Raquell de Castro Chaves ◽  
Auriana Serra Vasconcelos Mallmann ◽  
Natália Ferreira de Oliveira ◽  
Victor Celso Cavalcanti Capibaribe ◽  
Daniel Moreira Alves da Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Chronic Stress ◽  
Neuroprotective Effect

Dexmedetomidine reduced isoflurane neurotoxicity by preventing cytoskeletal depolymerization via the BDNF/RhoA signal pathway

2021 ◽  
Author(s):  
Liang Chi ◽  
Xiaoyang Yao ◽  
Caixia Gao ◽  
Huansheng Dong ◽  
huanqi Liu
Keyword(s):  
Mouse Model ◽  
Hippocampal Neurons ◽  
Water Maze ◽  
Critical Period ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Neurocognitive Deficits ◽  
Developing Neurons

Abstract Background Dexmedetomidine (Dex) has a significant neuroprotective effect in isoflurane-induced neurotoxicity during the critical period of synaptogenesis. However, the mechanisms by which Dex protects developing neurons are not clear. This research evaluated the protective effect of Dex against neuronal damage induced by isoflurane using a mouse model. Methods Neonatal Swiss mice at postnatal day 7 (PND7) were injected intraperitoneally with 15µg/kg, 20µg/kg, or 25µg/kg Dex, or normal saline, and then treated with 2% isoflurane for 2h. The results showed that 20µg/kg Dex could reduce isoflurane-induced neurocognitive deficits as assessed using the Morris water maze. The mechanisms by which Dex protected neurons were investigated using hippocampal neurons isolated from PND4-7 mice and exposed to 2% isoflurane (2h). Dex prevented cytoskeletal depolymerization that was induced by isoflurane. Results 15µg/ml Dex significantly reduced the percentage of apoptotic neurons. Dex reduced expression of activated caspase-3 in neurons compared to isoflurane only exposed mice. Using primary cell cultures from neonatal mouse hippocampi, we determined that dexmedetomidine could reverse isoflurane-induced RhoA (a small

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