Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate

Hirose, S; Umetani, Yukiko; Amitani, Misato; Hosoi, Rie; Momosaki, Sotaro; Hatazawa, Jun; Gee, Antony D.; Ito, Osamu

doi:10.1016/j.neulet.2007.01.031

Cited by 16 publications

(10 citation statements)

References 23 publications

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“…Fluorocitrate-induced glial inhibition results in a variety of metabolic effects including reduced ATP production and increased glucose metabolism (Fonnum et al, 1997; Hirose et al, 2007). Although not selectively affecting aconitase of different cellular origin per se , fluorocitrate primarily inhibits TCA cycle of astrocytes due to more avid uptake by astrocytes and has been used to assess the importance of glial cells for brain function in vivo (Fonnum et al, 1997; Zielke et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

Supraspinal Glial–Neuronal Interactions Contribute to Descending Pain Facilitation

Feng¹,

Guo²,

Zou³

et al. 2008

J. Neurosci.

272

281

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Section: Resultsmentioning

confidence: 99%

Supraspinal Glial–Neuronal Interactions Contribute to Descending Pain Facilitation

Feng¹,

Guo²,

Zou³

et al. 2008

J. Neurosci.

272

281

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“…Therefore, prolonged lack or impaired astrocyte functioning due to the FC-induced inhibition had to put also neurons under metabolic stress, although it did not kill them in the present experimental setting. FC has been shown previously to be predominantly taken up by glial cells through monocarboxylate transporter-1 and to inhibit the Krebs cycle enzyme aconitase, resulting in reduction of glial ATP production and overall metabolic stress [ 45 – 47 , 70 – 73 ]. Similarly to our data, selectivity of FC towards glial cells, without neuronal cell death, was proven before in a dose range up to 2 nmol after acute intrastriatal injection [ 45 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

Prolonged Dysfunction of Astrocytes and Activation of Microglia Accelerate Degeneration of Dopaminergic Neurons in the Rat Substantia Nigra and Block Compensation of Early Motor Dysfunction Induced by 6-OHDA

2017

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Progressive degeneration of dopaminergic neurons in the substantia nigra (SN) is the underlying cause of Parkinson’s disease (PD). The disease in early stages is difficult to diagnose, because behavioral deficits are masked by compensatory processes. Astrocytic and microglial pathology precedes motor symptoms. Besides supportive functions of astrocytes in the brain, their role in PD is unrecognized. Prolonged dysfunction of astrocytes could increase the vulnerability of dopaminergic neurons and advance their degeneration during aging. The aim of our studies was to find out whether prolonged dysfunction of astrocytes in the SN is deleterious for neuronal functioning and if it influences their survival after toxic insult or changes the compensatory potential of the remaining neurons. In Wistar rat model, we induced activation, prolonged dysfunction, and death of astrocytes by chronic infusion of fluorocitrate (FC) into the SN, without causing dopaminergic neuron degeneration. Strongly enhanced dopamine turnover in the SN after 7 days of FC infusion was induced probably by microglia activated in response to astrocyte stress. The FC effect was reversible, and astrocyte pool was replenished 3 weeks after the end of infusion. Importantly, the prolonged astrocyte dysfunction and microglia activation accelerated degeneration of dopaminergic neurons induced by 6-hydroxydopamine and blocked the behavioral compensation normally observed after moderate neurodegeneration. Impaired astrocyte functioning, activation of microglia, diminishing compensatory capability of the dopaminergic system, and increasing neuronal vulnerability to external insults could be the underlying causes of PD. This animal model of prolonged astrocyte dysfunction can be useful for in vivo studies of glia–microglia–neuron interaction.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-017-0529-z) contains supplementary material, which is available to authorized users.

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“…Infusion of fluorocitrare, a selective glial toxin, increased extracellular glutamate concentrations in the substantia nigra (Rodriguez Diaz et al 2004). In autoradiogram experiments, infusion of fluorocitrate into the striatum increased glucose uptake, which was attenuated by pretreatment with MK-801 (Hirose et al 2007), although it has been unclear whether the increased amount of glucose is metabolized aerobically or anaerobically (Hirose et al 2007). These considerations lead to the possibility that the increase in extracellular glutamate concentrations induced by DHK perfusion enhances glucose uptake and anaerobic metabolism of glucose.…”

Section: Discussionmentioning

confidence: 99%

Role of glutamate transporters in the modulation of stress-induced lactate metabolism in the rat brain

et al. 2007

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Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate

Cited by 16 publications

References 23 publications

Supraspinal Glial–Neuronal Interactions Contribute to Descending Pain Facilitation

Supraspinal Glial–Neuronal Interactions Contribute to Descending Pain Facilitation

Prolonged Dysfunction of Astrocytes and Activation of Microglia Accelerate Degeneration of Dopaminergic Neurons in the Rat Substantia Nigra and Block Compensation of Early Motor Dysfunction Induced by 6-OHDA

Role of glutamate transporters in the modulation of stress-induced lactate metabolism in the rat brain

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