Ceftriaxone modulates uptake activity of glial glutamate transporter‐1 against global brain ischemia in rats

Hu, Yu-Yan; Xu, Jing; Zhang, Min; Wang, Dan; Li, Li; Li, Wenbin

doi:10.1111/jnc.12958

Cited by 54 publications

(55 citation statements)

References 39 publications

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“…But how TSG exactly exerts neuronal protective effects remains obscure. It is well known that the injury of neurons in CNS disorders, such as Alzheimer's disease and brain ischemia, can be mediated by the impairment of astrocytic glutamate transporters [18,19]. In brain ischemia, the impairment astrocytic glutamate transporters would induce the over-accumulation of extracellular glutamate and then lead to the over-activation of glutamate receptors [20].…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that the injury of neurons in CNS disorders, such as Alzheimer's disease and brain ischemia, can be mediated by the impairment of astrocytic glutamate transporters [18,19]. In brain ischemia, the impairment astrocytic glutamate transporters would induce the over-accumulation of extracellular glutamate and then lead to the over-activation of glutamate receptors [20]. This effect of TSG on GLT-1 protein expression in cultured astrocytes provided another reasonable explanation for the protective mechanism of TSG in brain ischemia, and this mechanism may be more important than that observed in previous studies [11], as drugs targeting astrocytic glutamate transporters to enhance their expressions and functions have been considered potential therapeutics for CNS disorders for a long time [21].…”

Section: Discussionmentioning

confidence: 99%

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Mechanism of 2,3,4',5-Tetrahydroxystilbene 2-O-β-<smlcap>D</smlcap>-Glucoside-Induced Upregulation of Glutamate Transporter 1 Protein Expression in Mouse Primary Astrocytes

Chen¹,

Hu²,

Lu³

et al. 2017

Pharmacology

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Glutamate transporter-1 (GLT-1), a major glutamate transporter expressed in astrocytes, takes up excess glutamate from the micro-environment in order to prevent excitotoxicity. Drugs that increase GLT-1 expression may have therapeutic effects in disorders associated with neuronal excitotoxicity. 2,3,4',5-tetrahydroxystilbene 2-O-β-D-glucoside (TSG), a monomer of stilbene from polygonummultiflorum, exerts neuroprotection in a range of experimental models such as Alzheimer's disease and brain ischemia. In this study, we evaluated the effect of TSG on GLT-1 protein expression in mouse primary-cultured astrocytes. Results showed that TSG markedly increased the GLT-1 protein expression level in mouse primary-cultured astrocytes in a dose- and time-dependent manner, and this increase was mediated by the activation of protein kinase B (Akt) but not by the activation of extracellular signal-regulated protein kinase 1/2. Furthermore, inhibition of cAMP response element-binding protein, but not nuclear factor kappa B, abolished the TSG-mediated increase in GLT-1 protein expression in cultured astrocytes. Collectively, these findings may provide novel insights into the mechanism for TSG in neuroprotection, and would help search new agents targeting neurodegenerative disorders associated with impaired astrocytic glutamate transporters.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanism of 2,3,4',5-Tetrahydroxystilbene 2-O-β-<smlcap>D</smlcap>-Glucoside-Induced Upregulation of Glutamate Transporter 1 Protein Expression in Mouse Primary Astrocytes

Chen¹,

Hu²,

Lu³

et al. 2017

Pharmacology

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“…Later, reactive responses of astrocytes and microglia progress in parallel with the loss of motor neurons (Zhu et al, 2015). …”

Section: Astrocytes In the Diseased Brain Are Central To Neuropathologymentioning

confidence: 99%

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Liu

Teschemacher

Kasparov

2017

Glia

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Astrocytes are key homeostatic cells of the central nervous system. They cooperate with neurons at several levels, including ion and water homeostasis, chemical signal transmission, blood flow regulation, immune and oxidative stress defense, supply of metabolites and neurogenesis. Astroglia is also important for viability and maturation of stem‐cell derived neurons. Neurons critically depend on intrinsic protective and supportive properties of astrocytes. Conversely, all forms of pathogenic stimuli which disturb astrocytic functions compromise neuronal functionality and viability. Support of neuroprotective functions of astrocytes is thus an important strategy for enhancing neuronal survival and improving outcomes in disease states. In this review, we first briefly examine how astrocytic dysfunction contributes to major neurological disorders, which are traditionally associated with malfunctioning of processes residing in neurons. Possible molecular entities within astrocytes that could underpin the cause, initiation and/or progression of various disorders are outlined. In the second section, we explore opportunities enhancing neuroprotective function of astroglia. We consider targeting astrocyte‐specific molecular pathways which are involved in neuroprotection or could be expected to have a therapeutic value. Examples of those are oxidative stress defense mechanisms, glutamate uptake, purinergic signaling, water and ion homeostasis, connexin gap junctions, neurotrophic factors and the Nrf2‐ARE pathway. We propose that enhancing the neuroprotective capacity of astrocytes is a viable strategy for improving brain resilience and developing new therapeutic approaches.

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“…Thus, the in vitro model of aging cannot fully mimic the normal aging process. However, the results observed in this study may provide some important clues to better understand the mechanism of normal aging and neurodegeneration and better strategies for preventing and treating aging-related diseases, such as Alzheimer's disease and stroke [24,41,42] . In conclusion, this study demonstrates the activity-dependent down-regulation of TARPγ8 and GluA1 in prolonged neuronal culture, emphasizing a role of calpain.…”

Section: Ampa-induced Down-regulation Of Ampa-induced Currentsmentioning

confidence: 93%

Activity- and development-dependent down-regulation of TARPγ8 and GluA1 in cultured rat hippocampal neurons

Wang

et al. 2016

Acta Pharmacol Sin

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Aim: Transmembrane AMPA receptor regulatory proteins (TARPs) regulate the trafficking and expression of AMPA receptors that are essential for the fast excitatory synaptic transmission and plasticity in the brain. This study aimed to investigate the activity-dependent regulation of TARPγ8 in cultured rat hippocampal neurons. Methods: Rat hippocampal neurons cultured for 7-8 DIV or 17-18 DIV were exposed to the AMPA receptor agonist AMPA at a non-toxic concentration (100 μmol/L) for 4 h. The protein levels of TARPγ8 and AMPA receptor subunits (GluA1 and GluA2) were measured using Western blotting analysis. AMPA-induced currents were recorded in the neurons using a whole-cell recording method. Results: Four-hour exposure to AMPA significantly decreased the protein levels of TARPγ8 and GluA1 in the neurons at 17-18 DIV, but did not change the protein level of TARPγ8 in the neurons cultured at 7-8 DIV. AMPA-induced down-regulation of TARPγ8 and GluA1 was largely blocked by the calpain inhibitor calpeptin (50 μmol/L), but not affected by the caspase inhibitor zVAD (50 μmol/L). Fourhour exposure to AMPA significantly decreased AMPA-induced currents in the neurons at 17-18 DIV, which was blocked by co-exposure to calpeptin (50 μmol/L). Conclusion:The down-regulation of TARPγ8 and GluA1 protein levels and AMPA-induced currents in cultured rat hippocampal neurons is activity-and development-dependent, and mediated by endogenous calpain.

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Ceftriaxone modulates uptake activity of glial glutamate transporter‐1 against global brain ischemia in rats

Cited by 54 publications

References 39 publications

Mechanism of 2,3,4',5-Tetrahydroxystilbene 2-O-β-<smlcap>D</smlcap>-Glucoside-Induced Upregulation of Glutamate Transporter 1 Protein Expression in Mouse Primary Astrocytes

Mechanism of 2,3,4',5-Tetrahydroxystilbene 2-O-β-<smlcap>D</smlcap>-Glucoside-Induced Upregulation of Glutamate Transporter 1 Protein Expression in Mouse Primary Astrocytes

Astroglia as a cellular target for neuroprotection and treatment of neuro‐psychiatric disorders

Activity- and development-dependent down-regulation of TARPγ8 and GluA1 in cultured rat hippocampal neurons

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