Intracerebral microdialysis study of glutamate reuptake in awake, behaving rats

Alexander, Guillermo M.; Grothusen, John R.; Gordon, Susan J.; Schwartzman, Robert J.

doi:10.1016/s0006-8993(97)00519-2

Cited by 35 publications

(22 citation statements)

References 55 publications

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“…Other researchers have noted rapid rises in L-glutamate concentration during REM sleep [6,10] and active waking episodes [5]. L-Glutamate uptake has been shown to be inhibited by the infusion of L-glutamate via a microdialysis probe [21] and Kullmann et al [22] have demonstrated that released extracellular L-glutamate can spill-over and occupy neighboring synapses, thus eliciting further L-glutamate release. Taken together, these findings suggest that extracellular L-glutamate concentrations are continually rising during REM sleep while L-glutamate uptake is limited or hindered.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous real-time measurement of EEG/EMG and l-glutamate in mice: A biosensor study of neuronal activity during sleep

Naylor

Aillon

Gabbert

et al. 2011

Journal of Electroanalytical Chemistry

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We report on electroencephalograph (EEG) and electromyograph (EMG) measurements concurrently with real-time changes in L-glutamate concentration. These data reveal a link between sleep state and extracellular neurotransmitter changes in a freely-moving (tethered) mouse. This study reveals, for the first time in mice, that the extracellular L-glutamate concentration in the pre-frontal cortex (PFC) increases during periods of extended wakefulness, decreases during extended sleep episodes and spikes during periods of REM sleep. Individual sleep epochs (10 s in duration) were scored as wake, slow-wave (SW) sleep or rapid eye movement (REM) sleep, and then correlated as a function of time with measured changes in L-glutamate concentrations. The observed L-glutamate levels show a statistically significant increase of 0.86 ± 0.26 μM (p < 0.05) over 37 wake episodes recorded from all mice (n = 6). Over the course of 49 measured sleep periods longer than 15 min, L-glutamate concentrations decline by a similar amount (0.88 ± 0.37 μM, p < 0.08). The analysis of 163 individual REM sleep episodes greater than one min in length across all mice (n = 6) demonstrates a significant rise in L-glutamate levels as compared to the 1 min preceding REM sleep onset (RM-ANOVA, DF = 20, F = 6.458, p < 0.001). The observed rapid changes in L-glutamate concentration during REM sleep last only between 1 and 3 min. The approach described can also be extended to other regions of the brain which are hypothesized to play a role in sleep. This study highlights the importance of obtaining simultaneous measurements of neurotransmitter levels in conjunction with sleep markers to help elucidate the underlying physiological and ultimately the genetic components of sleep.

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Section: Resultsmentioning

confidence: 99%

Simultaneous real-time measurement of EEG/EMG and l-glutamate in mice: A biosensor study of neuronal activity during sleep

Naylor

Aillon

Gabbert

et al. 2011

Journal of Electroanalytical Chemistry

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“…Subtype-specific inactivation of the α 1 -adrenergic receptor has shown that the stimulatory effect is mediated by α 1b -adrenoceptor [43]. A phenylephrine-activated increase in clearance of glutamate from the extracellular space in rat brain has been confirmed in a microdialysis study [44]. Glutamine uptake in astrocytes is also enhanced by noradrenergic stimulation as indicated by an increase in the contents of both labeled glutamine and in its metabolites glutamate and aspartate after 30 min of exposure to [U-14 C]glutamine [255].…”

Section: Uptake and Release Of Amino Acidsmentioning

confidence: 78%

“…Since both glutamate uptake [41][42][43][44] and Na + ,K + -ATPase activity are increased [19], this stimulation could partly reflect an increase in energy-requiring processes. In addition adrenergic agonists exert a powerful direct effect on oxidative metabolism [45], probably to a large extent mediated by the evoked increase in [Ca 2+ ] i , and on glycogenolysis, mediated by protein kinase A (PKA) stimulation and/or the [Ca 2+ ] i effect [37,40].…”

Section: Introduction: Astrocytic Functionsmentioning

confidence: 99%

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

Hertz¹,

Chen²,

Gibbs³

et al. 2004

CDTCNSND

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Considerable attention has recently been paid to astrocyte functions, which are briefly summarized. A large amount of data is available about adrenoceptor expression and function in astrocytes, some of it dating back to the 1970's and some of it very recent. This material is reviewed in the present paper. The brain is innervated by noradrenergic fibers extending from locus coeruleus in the brain stem, which in turn is connected to a network of adrenergic and noradrenergic nuclei in the medulla and pons, contributing to the control of (nor)adrenergic, serotonergic, dopaminergic and cholinergic function, both in the central nervous system (CNS) and in the periphery. In the CNS astrocytes constitute a major target for noradrenergic innervation, which regulates morphological plasticity, energy metabolism, membrane transport, gap junction permeability and immunological responses in these cells. Noradrenergic effects on astrocytes are essential during consolidation of episodal, long-term memory, which is reinforced by β-adrenergic activation. Glycogenolysis and synthesis of glutamate and glutamine from glucose, both of which are metabolic processes restricted to astrocytes, occurs at several time-specific stages during the consolidation. Astrocytic abnormalities are almost certainly important in the pathogenesis of multiple sclerosis and in all probability contribute essentially to inflammation and malfunction in Alzheimer's disease and to mood disturbances in affective disorders. Noradrenergic function in astrocytes is severely disturbed by chronic exposure to cocaine, which also changes astrocyte morphology. Development of drugs modifying noradrenergic receptor activity and/or down-stream signaling is advocated for treatment of several neurological/psychiatric disorders and for neuroprotection. Astrocytic preparations are suggested for study of mechanism(s) of action of antidepressant drugs and pathophysiology of mood disorders.

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“…Under in vivo conditions in non-traumatized animals, intracerebral application of glutamate is dose-dependently cleared from the extracellular space (Alexander et al 1997) by active uptake mechanisms linked to increased lactate production (Demestre et al 1997).…”

Section: Discussionmentioning

confidence: 99%

Thiopental and midazolam do not seem to impede metabolism of glutamate in brain-injured patients

Stover

Pleines²,

Morganti-Kossmann³

et al. 1999

Psychopharmacology

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Increased extracellular glutamate levels are related to glial and neuronal damage. Glutamate-mediated toxicity is limited by glial uptake and metabolic transformation of glutamate to glutamine and the energetic compounds alanine and lactate which are utilized by surrounding neurons. Under in vitro conditions, barbiturates have been shown to reduce glutamate uptake and its further metabolism, possibly impeding metabolic coupling between astrocytes and neurons. The aims were to investigate if under clinical conditions, the barbiturate thiopental reduces important detoxification of glutamate, resulting in lower CSF glutamine, alanine and lactate levels as opposed to patients receiving midazolam. During long-term administration of thiopental and midazolam, pathologically elevated ventricular CSF glutamate levels were associated with significantly increased glutamine and alanine levels up to 14 days after trauma. CSF lactate, however, remained normal. These data suggest that long-term administration of thiopental and midazolam under clinical conditions does not impede enzymatic activities responsible for detoxification and metabolism of glutamate.

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Intracerebral microdialysis study of glutamate reuptake in awake, behaving rats

Cited by 35 publications

References 55 publications

Simultaneous real-time measurement of EEG/EMG and l-glutamate in mice: A biosensor study of neuronal activity during sleep

Simultaneous real-time measurement of EEG/EMG and l-glutamate in mice: A biosensor study of neuronal activity during sleep

Astrocytic Adrenoceptors: A Major Drug Target in Neurological and Psychiatric Disorders?

Thiopental and midazolam do not seem to impede metabolism of glutamate in brain-injured patients

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