Hypoxic-ischemic insult decreases glutamate uptake by hippocampal slices from neonatal rats: Prevention by guanosine

Moretto, Maria Beatriz; Arteni, Nice Sarmento; Lavinsky, Daniel; Netto, Carlos Alexandre; Rocha, João Batista Teixeira da; Souza, Diogo O.; Wofchuk, S.

doi:10.1016/j.expneurol.2005.06.005

Cited by 47 publications

(39 citation statements)

References 57 publications

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“…The effects of guanosine on the brain have been studied in a variety of experimental neuropathological protocols [3], including brain trauma [73], brain ischemia [13,17,18,74], and seizures [7,19]. These conditions may involve glutamatergic excitotoxicity, metabolic changes, and/or oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…Guanosine is released from astrocytes and confers neuroprotective effects in several in vivo and in vitro studies [3,[6][7][8][9][10][11]. Guanosine can effectively protect cells against hypoxia [12,13], cytotoxicity induced by the β-amyloid peptide [14], chronic cerebral hypoperfusion [15], ischemic insults [16][17][18], and other glutamatergic excitotoxic damage, such as seizures that are induced by quinolinic acid [3,9,19,20] and methylmercury-induced oxidative stress [21]. Although there is increasing evidence showing the neuroprotective effects of guanosine on models of neurotoxicity, its mechanisms are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Gliopreventive effects of guanosine against glucose deprivation in vitro

Quincozes‐Santos

Bobermin

Souza

et al. 2013

Purinergic Signalling

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Guanosine, a guanine-based purine, is recognized as an extracellular signaling molecule that is released from astrocytes and confers neuroprotective effects in several in vivo and in vitro studies. Astrocytes regulate glucose metabolism, glutamate transport, and defense mechanism against oxidative stress. C6 astroglial cells are widely used as an astrocyte-like cell line to study the astrocytic function and signaling pathways. Our previous studies showed that guanosine modulates the glutamate uptake activity, thus avoiding glutamatergic excitotoxicity and protecting neural cells. The goal of this study was to determine the gliopreventive effects of guanosine against glucose deprivation in vitro in cultured C6 cells. Glucose deprivation induced cytotoxicity, an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and lipid peroxidation as well as affected the metabolism of glutamate, which may impair important astrocytic functions. Guanosine prevented glucose deprivation-induced toxicity in C6 cells by modulating oxidative and nitrosative stress and glial responses, such as the glutamate uptake, the glutamine synthetase activity, and the glutathione levels. Glucose deprivation decreased the level of EAAC1, the main glutamate transporter present in C6 cells. Guanosine also prevented this effect, most likely through PKC, PI3K, p38 MAPK, and ERK signaling pathways. Taken together, these results show that guanosine may represent an important mechanism for protection of glial cells against glucose deprivation. Additionally, this study contributes to a more thorough understanding of the glial-and redox-related protective properties of guanosine in astroglial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gliopreventive effects of guanosine against glucose deprivation in vitro

Quincozes‐Santos

Bobermin

Souza

et al. 2013

Purinergic Signalling

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“…Figure 1 illustrates the kinetic characteristics of the Glu uptake process in hippocampal slices in both control and HF mice. Repeatedmeasures ANOVA revealed an effect of dietary treatment on Glu uptake velocity [F (1,24) HF diet upregulates the density of Glu transporters but downregulates the glucose transporter GLUT1. The effect of HF diets on the density of Glu transporters was examined in whole hippocampus by Western blot.…”

Section: Hf Diet Triggers Overweight and Increases Plasma Leptin Concmentioning

confidence: 99%

“…Glu uptake is carried out by specific neuronal (EAAT-3) and glial (GLT-1, GLAST) transporters, which display dynamic processes aimed at improving Glu clearance under conditions leading to increased release of Glu (27,34). Impairment of Glu uptake due to brain injury (24,28) or particular pathophysiological conditions, such as epileptic status (1), leads to the overstimulation of postsynaptic Glu receptors and triggers Glu-dependent excitotoxicity. In hippocampal and cortical circuits, Glu transmission accounts for learning and memory processes (5,8), and functional consequences of Glu-evoked neurotoxicity lead to cognitive disturbances (23).…”

mentioning

confidence: 99%

High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission

Valladolid‐Acebes¹,

Merino²,

Principato³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

135

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Valladolid-Acebes I, Merino B, Principato A, Fole A, Barbas C, Lorenzo MP, García A, Del Olmo N, Ruiz-Gayo M, Cano V. High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission. Am J Physiol Endocrinol Metab 302: E396 -E402, 2012. First published November 22, 2011; doi:10.1152/ajpendo.00343.2011.-Obesity and high-fat (HF) diets have a deleterious impact on hippocampal function and lead to impaired synaptic plasticity and learning deficits. Because all of these processes need an adequate glutamatergic transmission, we have hypothesized that nutritional imbalance triggered by these diets might eventually concern glutamate (Glu) neural pathways within the hippocampus. Glu is withdrawn from excitatory synapses by specific uptake mechanisms involving neuronal (EAAT-3) and glial (GLT-1, GLAST) transporters, which regulate the time that synaptically released Glu remains in the extracellular space and, consequently, the duration and location of postsynaptic receptor activation. The goal of the present study was to evaluate in mouse hippocampus the effect of a short-term high-fat dietary treatment on 1) Glu uptake kinetics, 2) the density of Glu carriers and Glu-degrading enzymes, 3) the density of Glu receptor subunits, and 4) synaptic transmission and plasticity. Here, we show that HF diet triggers a 50% decrease of the Michaelis-Menten constant together with a 300% increase of the maximal velocity of the uptake process. Glial Glu carriers GLT-1 and GLAST were upregulated in HF mice (32 and 27%, respectively), whereas Glu-degrading enzymes glutamine synthase and GABA-decarboxilase appeared to be downregulated in these animals. In addition, HF diet hippocampus displayed diminished basal synaptic transmission and hindered NMDAinduced long-term depression (NMDA-LTD). This was coincident with a reduced density of the NR2B subunit of NMDA receptors. All of these results are compatible with the development of leptin resistance within the hippocampus. Our data show that HF diets upregulate mechanisms involved in Glu clearance and simultaneously impair Glu metabolism. Neurochemical changes occur concomitantly with impaired basal synaptic transmission and reduced NMDA-LTD. Taken together, our results suggest that HF diets trigger neurochemical changes, leading to a desensitization of NMDA receptors within the hippocampus, which might account for cognitive deficits. obesity; electrophysiology; learning; long-term depression; glutamate uptake; leptin resistance GLUTAMATE (Glu) uptake is a pivotal process regulating excitatory transmission within the central nervous system, and its efficacy accounts for the time that released Glu remains in the extracellular space and, consequently, the duration of postsynaptic receptor activation. Glu uptake is carried out by specific neuronal (EAAT-3) and glial (GLT-1, GLAST) transporters, which display dynamic processes aimed at improving Glu clearance under conditions leading to increased release of Glu (27, 34). Impairment of Glu uptake due to brain injury (24, 28...

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“…Infarction of the entire hippocampus can develop if the global ischaemic insult is severe ( Figure 6) [10]. The fornix, cingulum and hippocampus can be simultaneously involved in severe global ischaemia (Figure 11) [11].…”

Section: Limbic Systemmentioning

confidence: 99%

Anatomical patterns and correlated MRI findings of non-perinatal hypoxic–ischaemic encephalopathy

White¹,

Zhang²,

Helvey³

et al. 2013

BJR

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ABSTRACT. Non-perinatal hypoxic-ischaemic encephalopathy (HIE) has varying anatomical patterns dependent on the type of insult, the degree and duration of cerebral hypoxia, or presence and degree of hypoperfusion. Profound insults can affect the entire cerebral cortex or just the perirolandic cortex, the cerebellum and the deep grey matter structures. Less severe insults may affect only the watershed regions. The objective of this article is to review the anatomical patterns of non-perinatal HIEs by MRI. Non-perinatal hypoxic-ischaemic encephalopathy (HIE) can be a devastating neurological injury and prompt recognition of it can result in significant changes in patient management. HIE insults develop in varying regions of the brain depending on the severity and duration of hypoperfusion or hypo-oxygenation [1]. Brain parenchyma changes have corresponding MR signal characteristics that are often obvious but can be subtle [2]. It is important for radiologists to be aware of the variations in the appearance of HIE in order to be alert to the diagnosis in subtle cases, recognise unusual patterns and be aware of the clinical ramifications.This review shows cases of HIE beyond the perinatal period. Aetiological factors and timing of imaging findings are delineated. The cases involve the usual HIE-specific neuroanatomical locations: the cerebral cortex, cerebellum, hippocampus, basal ganglia and thalamus. In addition, cases of HIE showing damage to the cerebral white matter and limbic system are demonstrated. Also, cases that mimic the appearance of HIE are presented. It is critical for a radiologist to be aware of potentially confounding cases.

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Hypoxic-ischemic insult decreases glutamate uptake by hippocampal slices from neonatal rats: Prevention by guanosine

Cited by 47 publications

References 57 publications

Gliopreventive effects of guanosine against glucose deprivation in vitro

Gliopreventive effects of guanosine against glucose deprivation in vitro

High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission

Anatomical patterns and correlated MRI findings of non-perinatal hypoxic–ischaemic encephalopathy

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