INT155683

Context Info Confidence 0.73 First Reported 2006 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 27 Total Number 29 Disease Relevance 9.86 Pain Relevance 15.34

transport (Slc1a2) plasma membrane (Slc1a2)

Anatomy Link Frequency neuronal 3 brain 3 whisker 3 cerebrum 2 astrocyte 2 Slc1a2 (Mus musculus)

Pain Link Frequency Relevance Heat Glutamate 962 100.00 nMDA receptor 25 100.00 excitatory amino acid 16 100.00 Physical dependence 12 99.20 Hippocampus 58 98.92 tolerance 30 98.72 Morphine 45 98.70 primary somatosensory cortex 14 98.16 analgesia 21 98.10 addiction 18 96.96

Disease Link Frequency Relevance Heat Congenital Anomalies 9 99.92 Injury 415 99.74 Penetrating Head Injuries 30 99.70 Brain Injury 60 99.64 Stab Wounds 90 99.60 Epilepsy 28 99.22 Targeted Disruption 236 99.20 Drug Dependence 12 99.20 Neurological Disease 3 98.80 Suicidal Behaviour 1 97.92

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Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Using Western blot analysis on single barrel columns corresponding to the stimulated whisker, we found that expression levels of GLT1 and GLAST were significantly increased.

Gene_expression (expression) of GLT1 in whisker

1) Confidence 0.73 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0.15 Pain Relevance 0.27

All the evidence supports the idea that regulating the expression of GLT1 and GLAST during a period of increased glutamate release, e.g., during increased sensory stimulation, is necessary for avoiding any effects of glutamate build-up.

Gene_expression (expression) of GLT1 associated with glutamate

2) Confidence 0.73 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0.09 Pain Relevance 0.34

On a longer time scale, however, the expression levels of GLT1 and GLAST have been shown, in vitro, to depend on the level of neuronal activity [14].

Gene_expression (expression) of GLT1 in neuronal

3) Confidence 0.73 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0.08 Pain Relevance 0.35

Increase in epileptic activity has also been seen when only GLT1 expression is lowered [34,35].

Gene_expression (expression) of GLT1 associated with epilepsy

4) Confidence 0.73 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0.10 Pain Relevance 0.33

Western blot analysis (Figure 1C and 1D) shows that after 24 h of whisker stimulation, GLAST and GLT1 expression increased 2.46-fold and 2.65-fold of the unstimulated value (GLAST: 246 ± 20.9% mean ± standard deviation [SD]; GLT1: 265 ± 38.1%; p < 0.01, Tukey honestly significant difference [HSD]).

Gene_expression (expression) of GLT1 in whisker

5) Confidence 0.73 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0 Pain Relevance 0.07

SLC1A2 is the predominant transporter expressed in the plasma membrane of hippocampus glial cells [57].

Gene_expression (expressed) of SLC1A2 in glial cells associated with hippocampus

6) Confidence 0.73 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2896956 Disease Relevance 0.15 Pain Relevance 0.37

This suggested that AQP4 deficiency inhibited the development of morphine physical dependence. (4) Repeated morphine administration down-regulated cerebral glutamate transporter 1 (GLT-1) expression in wild-type mice.

Gene_expression (expression) of GLT-1 associated with glutamate, physical dependence and morphine

7) Confidence 0.69 Published 2008 Journal Neurosci. Lett. Section Abstract Doc Link 18973795 Disease Relevance 0.59 Pain Relevance 2.02

The suppression of down-regulation of cerebral GLT1 expression might mediate the attenuation of AQP4 deficiency to morphine tolerance and dependence.

Gene_expression (expression) of GLT1 associated with addiction, tolerance and morphine

8) Confidence 0.69 Published 2008 Journal Neurosci. Lett. Section Abstract Doc Link 18973795 Disease Relevance 0.54 Pain Relevance 1.67

However, the down-regulation of GLT-1 expression diminished in AQP4 knockout mice.

Gene_expression (expression) of GLT-1 associated with targeted disruption

9) Confidence 0.69 Published 2008 Journal Neurosci. Lett. Section Abstract Doc Link 18973795 Disease Relevance 0.58 Pain Relevance 1.94

GLT1 and actin, or EAAC1 and actin (Figure 1) were first detected, followed by stripping of the membrane and reprobing for GLAST or tubulin, respectively.

Gene_expression (detected) of GLT1

10) Confidence 0.64 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0 Pain Relevance 0

GLT1, GLAST, and EAAC1 levels were normalized to actin.

Gene_expression (levels) of GLT1

11) Confidence 0.64 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0 Pain Relevance 0.05

Using mice, we found that 24 h of whisker stimulation elicited a 2-fold increase in the expression of GLT1 and GLAST in the corresponding cortical column of the barrel cortex.

Gene_expression (expression) of GLT1 in barrel cortex

12) Confidence 0.57 Published 2006 Journal PLoS Biology Section Abstract Doc Link PMC1609127 Disease Relevance 0 Pain Relevance 0.26

On a longer time scale, however, the expression levels of GLT1 and GLAST have been shown, in vitro, to depend on the level of neuronal activity [14].

Gene_expression (levels) of GLT1 in neuronal

13) Confidence 0.57 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0.08 Pain Relevance 0.35

This function of the astrocyte is dependent on its positioning around the synapse, as well as on the level of expression of its high-affinity glutamate transporters, GLT1 and GLAST.

Gene_expression (expression) of GLT1 in astrocyte associated with glutamate

14) Confidence 0.57 Published 2006 Journal PLoS Biology Section Abstract Doc Link PMC1609127 Disease Relevance 0 Pain Relevance 0.21

Using Western blot analysis on single barrel columns corresponding to the stimulated whisker, we found that expression levels of GLT1 and GLAST were significantly increased.

Gene_expression (levels) of GLT1 in whisker

15) Confidence 0.57 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0.15 Pain Relevance 0.27

Louis, Missouri, United States), actin (1:2,000; Roche, Basel, Switzerland), polyclonal: GLT1 (0.05 ?

Gene_expression (0.05) of GLT1

16) Confidence 0.55 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0 Pain Relevance 0

Louis, Missouri, United States), actin (1:2,000; Roche, Basel, Switzerland), polyclonal: GLT1 (0.05 ?

Gene_expression (Louis) of GLT1

17) Confidence 0.55 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1609127 Disease Relevance 0 Pain Relevance 0

To assess the functional state of astrocytes after traumatic brain injury, we analyzed the expression of two glutamate transporters, glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1/EAAT2), the glutamate transaminase, glutamine synthetase (GS) and the calcium regulatory protein S-100B.

Spec (analyzed) Gene_expression (expression) of EAAT2 in brain associated with glutamate and brain injury

18) Confidence 0.54 Published 2006 Journal J Neuroinflammation Section Body Doc Link PMC1533808 Disease Relevance 0.65 Pain Relevance 0.24

Our results show that in both WT and receptor-null mice, stab wound injury increased GLAST, GLT-1, GS and S-100B protein expression at 3 day post injury by 8, 6, 4 and 12 fold, respectively (Fig. 7).

Gene_expression (expression) of GLT-1 associated with injury and stab wounds

19) Confidence 0.54 Published 2006 Journal J Neuroinflammation Section Body Doc Link PMC1533808 Disease Relevance 0.44 Pain Relevance 0.28

To assess the functional state of astrocytes after traumatic brain injury, we analyzed the expression of two glutamate transporters, glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1/EAAT2), the glutamate transaminase, glutamine synthetase (GS) and the calcium regulatory protein S-100B.

Spec (analyzed) Gene_expression (expression) of GLT-1 in brain associated with glutamate and brain injury

20) Confidence 0.54 Published 2006 Journal J Neuroinflammation Section Body Doc Link PMC1533808 Disease Relevance 0.65 Pain Relevance 0.24

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