INT88789

Context Info Confidence 0.78 First Reported 2000 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 26 Total Number 36 Disease Relevance 4.41 Pain Relevance 12.74

plasma membrane (Dlg4) protein complex assembly (Dlg4) response to stress (Dlg4) cytoplasm (Dlg4)

Anatomy Link Frequency spinal cord 4 neurons 4 plasma 3 tail 2 brain 2 Dlg4 (Rattus norvegicus)

Pain Link Frequency Relevance Heat depression 6 100.00 Spinal cord 112 99.98 fluoxetine 24 99.98 Morphine 54 99.44 nMDA receptor 52 99.32 addiction 67 98.48 Hippocampus 17 98.04 Central nervous system 43 97.92 Thermal hyperalgesia 11 97.92 tail-flick 12 97.40

Disease Link Frequency Relevance Heat Depression 6 100.00 Infection 11 99.80 Morphine Dependence 12 98.84 Hyperalgesia 19 97.92 Targeted Disruption 3 96.72 Schizophrenia 2 93.64 Injury 5 90.28 Stress 11 87.32 Neuropathic Pain 13 85.28 Nervous System Injury 4 83.44

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Key:

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Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Co-administration of morphine twice daily and PSD-95 antisense oligodeoxynucleotide (50 microg/10 microl) once daily for 4 days not only markedly reduced the PSD-95 expression and its binding to NMDA receptors in spinal cord but also significantly prevented the development of morphine tolerance.

Gene_expression (expression) of PSD-95 in spinal cord associated with nmda receptor, tolerance, spinal cord and morphine

1) Confidence 0.78 Published 2004 Journal Neuroscience Section Abstract Doc Link 14667437 Disease Relevance 0 Pain Relevance 1.29

OBJECTIVE: To observe the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density-95 (PSD-95) in hippocampal CA1 region of rat with morphine dependence for different times and withdrawn for 1 week, and investigate the influence of that morphine dependence is withdrawn on rat hippocampal CA1 area.

Gene_expression (expression) of PSD-95 in brain associated with addiction and morphine

2) Confidence 0.77 Published 2008 Journal Sichuan Da Xue Xue Bao Yi Xue Ban Section Abstract Doc Link 18630696 Disease Relevance 0.19 Pain Relevance 0.36

RESULTS: The expression of BDNF and PSD-95 in hippocampal CA1 decreased in the withdrawn group with morphine dependence for 1 week as compared with that in normal saline (NS) group (P < 0.01), and it increased in the withdrawn group with morphine dependence for 2 weeks as compared with that in morphine-dependent group for 1 week (P < 0.05) but still decreased as compared with that in NS group (P < 0.01), and it decreased in the withdrawn group with morphine dependence for 4 weeks as compared with the other three groups (P < 0.01).

Gene_expression (expression) of PSD-95

3) Confidence 0.77 Published 2008 Journal Sichuan Da Xue Xue Bao Yi Xue Ban Section Body Doc Link 18630696 Disease Relevance 0.09 Pain Relevance 0

[The expression of BDNF and PSD-95 in hippocampal CA1 region of morphine-withdrawn rat with different dependent times].

Gene_expression (expression) of PSD-95 associated with morphine

4) Confidence 0.77 Published 2008 Journal Sichuan Da Xue Xue Bao Yi Xue Ban Section Title Doc Link 18630696 Disease Relevance 0.09 Pain Relevance 0.36

The expression of BDNF and PSD-95 in hippocampal CA1 were identified with RT-PCR.

Gene_expression (expression) of PSD-95

5) Confidence 0.77 Published 2008 Journal Sichuan Da Xue Xue Bao Yi Xue Ban Section Body Doc Link 18630696 Disease Relevance 0.09 Pain Relevance 0

CONCLUSION: The expression of BDNF and PSD-95 in hippocampal CA1 decreases in morphine-depended rats withdrawn for 1 week.

Gene_expression (expression) of PSD-95

6) Confidence 0.77 Published 2008 Journal Sichuan Da Xue Xue Bao Yi Xue Ban Section Body Doc Link 18630696 Disease Relevance 0.07 Pain Relevance 0

OBJECTIVE: To observe the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density-95 (PSD-95) in hippocampal CA1 region of rat with morphine dependence for different times and withdrawn for 1 week, and investigate the influence of that morphine dependence is withdrawn on rat hippocampal CA1 area.

Gene_expression (expression) of postsynaptic density-95 in brain associated with addiction and morphine

7) Confidence 0.77 Published 2008 Journal Sichuan Da Xue Xue Bao Yi Xue Ban Section Abstract Doc Link 18630696 Disease Relevance 0.19 Pain Relevance 0.36

It was thus necessary to verify that the activity recorded through the electrodes faithfully represented the activity of those neurons expressing PSD-95:GFP and followed by time-lapse microscopy.

Gene_expression (expressing) of PSD-95 in neurons

8) Confidence 0.76 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0.09 Pain Relevance 0

PSDs were visualized by expressing an EGFP-tagged variant of the PSD molecule PSD-95 (PSD-95:GFP).

Gene_expression (expressing) of PSD-95

9) Confidence 0.76 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0.12

Furthermore, due to the random nature of lentiviral infection, neurons expressing PSD-95:GFP were not necessarily located over any particular electrode.

Gene_expression (expressing) of PSD-95 in neurons associated with infection

10) Confidence 0.67 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0.10 Pain Relevance 0

For example, in the first study mentioned above, PSD-95:GFP expression levels were reported to be many fold greater than endogenous PSD-95 levels, whereas the use of Sindbis or Semliki forest viral vectors for PSD-95:GFP expression in others might have resulted in similar situations [72].

Gene_expression (expression) of PSD-95

11) Confidence 0.66 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0

Furthermore, PSD-95:GFP overexpression was previously shown to affect synaptic properties and even occlude forms of activity-induced synaptic plasticity [67]–[71].

Gene_expression (overexpression) of PSD-95

12) Confidence 0.66 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0.03

Given the low PSD-95:GFP expression levels here and the fact that the aforementioned forms of synaptic plasticity were not occluded in our system, it seems unlikely that the phenomena described here are solely artifacts of PSD-95:GFP overexpression, although, as mentioned above, we cannot exclude the possibility of the introduction of some quantitative inaccuracies [79].

Gene_expression (expression) of PSD-95

13) Confidence 0.66 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0.05

A potential concern is the use of an exogenous form of PSD-95 fused to EGFP (an ?

Gene_expression (fused) of PSD-95

14) Confidence 0.66 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0.04

These experiments strongly indicate that the characteristics of network activity recorded through the MEA faithfully represent, at least to a first approximation, the activity of PSD-95:GFP-expressing neurons.

Gene_expression (expressing) of PSD-95 in neurons

15) Confidence 0.66 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0.06 Pain Relevance 0

Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREB(Serine-133), and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14).

Gene_expression (expression) of PSD-95 associated with depression and morphine

16) Confidence 0.63 Published 2006 Journal Hippocampus Section Abstract Doc Link 16598705 Disease Relevance 0.27 Pain Relevance 0.93

Furthermore, the tight correlation between network bursts and calcium transients suggests that these neurons respond well to excitatory synapse activation, implying that PSD-95:GFP expression does not severely impair glutamatergic synapse functionality.

Gene_expression (expression) of PSD-95 in synapse

17) Confidence 0.59 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0.05 Pain Relevance 0

This remodeling is not an artifact of imaging-related noise because practically no change in M was observed in control experiments performed in exactly the same experimental conditions using paraformaldehyde-fixed, PSD-95:GFP-expressing neurons (Figure 8A and 8B).

Gene_expression (expressing) of PSD-95 in neurons associated with imagery

18) Confidence 0.59 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0.09 Pain Relevance 0.38

For example, in the first study mentioned above, PSD-95:GFP expression levels were reported to be many fold greater than endogenous PSD-95 levels, whereas the use of Sindbis or Semliki forest viral vectors for PSD-95:GFP expression in others might have resulted in similar situations [72].

Gene_expression (levels) of PSD-95

19) Confidence 0.58 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0

The rats injected intrathecally with postsynaptic density protein-95 antisense oligodeoxynucleotide every 24 h for 4 days from day 7 to day 10 post-surgery exhibited not only a marked decrease in spinal cord postsynaptic density protein-95 protein expression but also a significant reduction in mechanical and thermal hyperalgesia on day 11 post-surgery.

Gene_expression (expression) of postsynaptic density protein-95 in spinal cord associated with thermal hyperalgesia and spinal cord

20) Confidence 0.52 Published 2003 Journal Neuroscience Section Abstract Doc Link 12617977 Disease Relevance 0.75 Pain Relevance 0.65

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