The age-related changes and differences in energy metabolism and glutamate-glutamine recycling in the d-gal-induced and naturally occurring senescent astrocytes in vitro

Cao, Peiguo; Zhang, Jingjing; Huang, Yuyan; Fang, Yujia; Lyu, Jianxin; Shen, Yao

doi:10.1016/j.exger.2018.12.018

Cited by 25 publications

(16 citation statements)

References 31 publications

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“…However, recent studies demonstrated that glycolysis increased with a decline in the resting cerebral blood flow of the aged brain ( Lourenço et al, 2017 ). It also increased in naturally aging astrocytes ( Cao et al, 2019 ). Furthermore, glycolysis dysfunction can lead to age-related neurodegeneration ( Hipkiss, 2019 ).…”

Section: Glycolysis Dysfunctionmentioning

confidence: 99%

Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

Wang

et al. 2020

Front. Neurosci.

126

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Alzheimer's disease (AD) is an incurable neurodegenerative disease. Numerous studies have demonstrated a critical role for dysregulated glucose metabolism in its pathogenesis. In this review, we summarize metabolic alterations in aging brain and ADrelated metabolic deficits associated with glucose metabolism dysregulation, glycolysis dysfunction, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) deficits, and pentose phosphate pathway impairment. Additionally, we discuss recent treatment strategies targeting metabolic defects in AD, including their limitations, in an effort to encourage the development of novel therapeutic strategies.

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Section: Glycolysis Dysfunctionmentioning

confidence: 99%

Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

Wang

et al. 2020

Front. Neurosci.

126

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“…Neuroinflammation acts as the contributor in accelerating the pathological progression of aging-related neurodegenerative diseases, and the increasing researches have demonstrated that chronic D-gal administration can stimulate the microglia and astrocytes activation in central nervous system, thereby inducing chronic neuroinflammation ( Lu et al, 2010 ; Cao et al, 2019 ; Yahfoufi et al, 2020 ). Therefore, in this study, we measured the contents of TNF-α, IL-1β, and IL-6 in the hippocampus through ELISA.…”

Section: Resultsmentioning

confidence: 99%

Qiangji Decoction Alleviates Neurodegenerative Changes and Hippocampal Neuron Apoptosis Induced by D-Galactose via Regulating AMPK/SIRT1/NF-κB Signaling Pathway

Wang

et al. 2021

Front. Pharmacol.

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Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging–related neurodegenerative diseases. However, the mechanisms underlying QJD’s improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose subcutaneous injection. Next, we investigated QJD’s effect on cognitive function of the model of brain aging and the mechanisms that QJD suppressing neuroinflammation as well as improving neurodegenerative changes and hippocampal neuron apoptosis. The mice of brain aging were treated with three different dosages of QJD (12.48, 24.96, and 49.92 g/kg/d, respectively) for 4 weeks. Morris water maze was used to determine the learning and memory ability of the mice. HE staining and FJB staining were used to detect the neurodegenerative changes. Nissl staining and TUNEL staining were employed to detect the hippocampal neuron apoptosis. The contents of TNF-α, IL-1β, and IL-6 in the hippocampus were detected by using ELISA. Meanwhile, we employed immunofluorescence staining to examine the levels of GFAP and IBA1 in the hippocampus. Besides, the protein expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, AMPKα, p-AMPKα-Thr172, SIRT1, IκBα, NF-κB p65, p-IκBα-Ser32, and p-NF-κB p65-Ser536 in the hippocampus of different groups were detected by Western blot (WB). Our findings showed that the QJD-treated groups, especially the M-QJD group, mitigated learning and memory impairments of the model of brain aging as well as the improvement of neurodegenerative changes and hippocampal neuron apoptosis. Moreover, the M-QJD markedly attenuated the neuroinflammation by regulating the AMPK/SIRT1/NF-κB signaling pathway. Taken together, QJD alleviated neurodegenerative changes and hippocampal neuron apoptosis in the model of brain aging via regulating the AMPK/SIRT1/NF-κB signaling pathway.

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“…Besides, it was demonstrated that astrocytes exhibited eventual growth arrest at late passages of in vitro culturing compared to early passages, indicating replicative senescence from primary astrocytes [21,22]. Astrocytes have also been documented to undergo stress-induced premature senescence [23][24][25]. Therefore, astrocytes have been displayed to undergo cellular senescence in vitro due to a variety of factors such as replicative lifespan or external stressors.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease

Xia

Xie

Ding

et al. 2020

J Neuroinflammation

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Background: Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson's disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined.Methods: Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP + )-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers. Results:We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP + -induced premature senescence, evidenced by decreased senescence-associated β-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence. Conclusions: Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.

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The age-related changes and differences in energy metabolism and glutamate-glutamine recycling in the d-gal-induced and naturally occurring senescent astrocytes in vitro

Cited by 25 publications

References 31 publications

Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

Qiangji Decoction Alleviates Neurodegenerative Changes and Hippocampal Neuron Apoptosis Induced by D-Galactose via Regulating AMPK/SIRT1/NF-κB Signaling Pathway

Astragaloside IV inhibits astrocyte senescence: implication in Parkinson’s disease

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