Age and meloxicam modify the response of the glutamate vesicular transporters (VGLUTs) after transient global cerebral ischemia in the rat brain

Llorente, Irene L.; Pérez‐Rodríguez, Diego; Burgin, Taiana C.; Orden, José Manuel Gonzalo; Martínez-Villayandre, Beatriz; Fernández‐López, Arsenio

doi:10.1016/j.brainresbull.2013.02.006

Cited by 23 publications

(19 citation statements)

References 45 publications

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“…, b, c, ; Llorente et al . ). These data suggest that I/R results in a decrease in neurotransmission in both excitatory (glutamatergic) and inhibitory (GABAergic) systems, while it activates the UPR to reduce the cellular damage resulting from the insult.…”

Section: Discussionmentioning

confidence: 97%

Unfolded protein response to global ischemia following 48 h of reperfusion in the rat brain: the effect of age and meloxicam

Llorente

Burgin

Pérez‐Rodríguez

et al. 2013

Journal of Neurochemistry

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The unfolded protein response (UPR) in the hippocampal regions Cornu Ammonis 1 hippocampal region, Cornu Ammonis 3 hippocampal region, and dentate gyrus, as well as in the cerebral cortex of 3-month-old and 18-month-old rats were studied in a model of 15 min of global cerebral ischemia followed by 48 h of reperfusion. UPR was measured by quantifying the protein disulfide isomerase (PDI), C/EBPhomologous protein (CHOP), GRP78 and GRP94 transcripts using qPCR and the amounts of PDI and GRP78 by western blot. The study shows how the mRNA levels of these genes were similar in 3-month-old and 18-month-old sham-operated animals, but the ischemic insult elicited a noticeable increase in the expression of these genes in young animals that was scarcely appreciable in older animals. The striking increase in the mRNA levels of these genes in 3-month-old animals was abolished or even reverted by treatment with meloxicam, an anti-inflammatory agent. Western blot assays showed that the UPR was still detectable 48 h after ischemia in some of the studied areas, and provided evidence that the UPR is different between young and older animals. Western blot assays carried out in young animals also showed that meloxicam elicited different effects on the levels of PDI and GRP78 in the cerebral cortex and the hippocampus. We conclude that the UPR response to ischemic/reperfusion insult is age-and probably inflammation-dependent and could play an important role in ischemic vulnerability. The UPR appears to be strongly decreased in aged animals, suggesting a reduced ability for cell survival.

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Section: Discussionmentioning

confidence: 97%

Unfolded protein response to global ischemia following 48 h of reperfusion in the rat brain: the effect of age and meloxicam

Llorente

Burgin

Pérez‐Rodríguez

et al. 2013

Journal of Neurochemistry

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“…Previous studies allow us to estimate that we could detect changes at p ≤ 0.05 level with a statistical power of ≥ 80% with n ≥ 5 rats/ group (Llorerente et al ; Llorerente et al ; Anuncibay‐Soto et al ; Ugidos et al ; Anuncibay‐Soto et al ). Thus, prior to experimental procedure, the number of animals to be used in each group was established in five.…”

Section: Methodsmentioning

confidence: 92%

Post‐ischemic salubrinal administration reduces necroptosis in a rat model of global cerebral ischemia

Font‐Belmonte

Ugidos

Santos‐Galdiano

et al. 2019

Journal of Neurochemistry

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Ischemic stroke is one of the most important causes of death and disability worldwide. Subroutines underlying cell death after stroke are largely unknown despite their importance in the design of novel therapies for this pathology. Necroptosis, a recently described form of regulated cell death, has been related with inflammation and, in some models, with endoplasmic reticulum (ER) stress. We hypothesize that alleviation of ER stress following a salubrinal treatment will reduce the ischemic‐dependent necroptosis. To probe the hypothesis, we measured, at 48 and 72 h after transient global cerebral ischemia in rat, in cerebral cortex and cornu ammonis 1, the main hallmarks of necroptosis: mRNA levels and phosphorylation of mixed lineage kinase domain like pseudokinase as well as receptor interacting serine/threonine protein kinase 3, along the years 2017–2018. Selective neuronal loss after 7 days of the ischemic insult, and other markers related with the inflammatory response were also measured. This study shows that necroptosis in cerebral cortex can be detected after 72 h of the insult and seems to be elicited before 48 h of reperfusion. The type of necroptosis here observed seems to be tumor necrosis factor receptor 1 independent. Necroptotic response is less evident in the cornu ammonis 1 hippocampal area than in cerebral cortex. The treatment with salubrinal administered 1 and 24 h after the ischemia, decreased the necroptotic marker levels and reduced the areas of selective neuronal loss, supporting the presence of ischemic‐dependent necroptosis, and the notion that ER stress is involved in the necroptotic response. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/

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“…Interestingly, the VGLUT2 protein level in adult animals was lower after ischemia in CA3 hippocampal region, dentate gyrus and cortex, but higher in the CA1 compared with the control. VGLUT3 mRNA was reduced in all areas after focal ischemia [187] . These findings suggested that changes in the expression of VGLUT proteins, following focal cerebral ischemia, are age-related.…”

Section: Vgluts In Ischemic Brainmentioning

confidence: 97%

“…However, other studies did not show any changes in VGLUT1 expression after focal cerebral ischemia, while VGLUT2 and VGLUT3 mRNAs were downregulated [186] . Another study on focal cerebral ischemia demonstrated reduction in mRNA level of VGLUT1-3 in the hippocampus and cerebral cortex of young rats [187] , suggesting an age-dependent modification in VGLUTs expression. Indeed, in young animals the level of VGLUT1 protein was reduced in the hippocampus and cortex, whereas VGLUT2 protein level was increased in these structures, but reduced in the dentate gyrus.…”

Section: Vgluts In Ischemic Brainmentioning

confidence: 99%

Glutamate transporters in brain ischemia: to modulate or not?

et al. 2014

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In this review, we briefly describe glutamate (Glu) metabolism and its specific transports and receptors in the central nervous system (CNS). Thereafter, we focus on excitatory amino acid transporters, cystine/glutamate antiporters (system x c -) and vesicular glutamate transporters, specifically addressing their location and roles in CNS and the molecular mechanisms underlying the regulation of Glu transporters. We provide evidence from in vitro or in vivo studies concerning alterations in Glu transporter expression in response to hypoxia or ischemia, including limited human data that supports the role of Glu transporters in stroke patients. Moreover, the potential to induce brain tolerance to ischemia through modulation of the expression and/or activities of Glu transporters is also discussed. Finally we present strategies involving the application of ischemic preconditioning and pharmacological agents, eg β-lactam antibiotics, amitriptyline, riluzole and N-acetylcysteine, which result in the significant protection of nervous tissues against ischemia.

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Age and meloxicam modify the response of the glutamate vesicular transporters (VGLUTs) after transient global cerebral ischemia in the rat brain

Cited by 23 publications

References 45 publications

Unfolded protein response to global ischemia following 48 h of reperfusion in the rat brain: the effect of age and meloxicam

Unfolded protein response to global ischemia following 48 h of reperfusion in the rat brain: the effect of age and meloxicam

Post‐ischemic salubrinal administration reduces necroptosis in a rat model of global cerebral ischemia

Glutamate transporters in brain ischemia: to modulate or not?

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