INT97099

Context Info Confidence 0.60 First Reported 2001 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 13 Total Number 17 Disease Relevance 3.04 Pain Relevance 6.98

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

Anatomy Link Frequency neuronal 2 shell 2 synapse 2 nucleus accumbens 1 descending colon 1 Dlg4 (Rattus norvegicus)

Pain Link Frequency Relevance Heat gABA 17 100.00 dopamine receptor 6 99.90 Morphine 27 99.84 nMDA receptor 19 99.80 Nucleus accumbens 22 99.68 fluoxetine 8 99.32 Thermal hyperalgesia 8 98.88 Spinal cord 2 97.16 Action potential 26 95.80 Glutamate receptor 19 93.64

Disease Link Frequency Relevance Heat Hyperalgesia 8 98.88 Apoptosis 43 98.02 Targeted Disruption 7 95.40 Pain 2 92.88 Cv Unclassified Under Development 12 92.40 Stress 28 90.16 Nervous System Injury 4 85.44 Neuropathic Pain 8 83.76 Ganglion Cysts 14 82.84 Death 24 78.80

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

As the majority of PSD-95:GFP puncta were typically juxtaposed against functional presynaptic boutons (Figure S1; see also [35]), the observed increases in PSD-95:GFP puncta number reflected, in all likelihood, increased numbers of glutamatergic synapses.

Positive_regulation (increases) of PSD-95 in synapses

1) Confidence 0.60 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0.04

An interesting finding was the observation that high levels of network activity were associated with gradual increases in PSD-95:GFP puncta numbers, whereas suppressed activity levels were associated with gradual decreases in PSD-95:GFP puncta numbers (see also [82],[83]).

Positive_regulation (increases) of PSD-95

2) Confidence 0.60 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0.06 Pain Relevance 0

Our previous work has shown that PSD-95/SAP90 is required for NMDA receptor-mediated thermal hyperalgesia.

Positive_regulation (required) of PSD-95 associated with thermal hyperalgesia and nmda receptor

3) Confidence 0.50 Published 2001 Journal Neuroreport Section Abstract Doc Link 11711866 Disease Relevance 0.70 Pain Relevance 0.62

CONCLUSION: The results indicate not only a significant decrease in MAC for isoflurane but also an attenuation in the NMDA-induced increase in isoflurane MAC in the PSD-95/SAP90 antisense-treated animals, which suggests that PSD-95/SAP90 may mediate the role of the NMDA receptor in determining the MAC of inhalational anesthetics.

Positive_regulation (increase) of PSD-95

4) Confidence 0.50 Published 2001 Journal Anesthesiology Section Body Doc Link 11465592 Disease Relevance 0 Pain Relevance 0

To determine whether the observed changes in PSD-95:GFP puncta number and fluorescence intensity were dependent on changes in network activity, we repeated the experiments described above except that here, spontaneous network activity was blocked by adding tetrodotoxin (TTX) about an hour after the experiments were started.

Positive_regulation (changes) of PSD-95 associated with tetrodotoxin

5) Confidence 0.43 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0.06 Pain Relevance 0.18

In practically all experiments, we observed a gradual increase in the total number of PSD-95:GFP puncta, mainly (but not exclusively) due to increased density of PSD-95:GFP puncta along existing dendritic segments, at both spine tips and shafts (Figures 1C and 3B).

Positive_regulation (increase) of PSD-95 in shafts

6) Confidence 0.40 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0.10

Our findings that suppression of activity broadens the distribution of PSD-95:GFP puncta fluorescence intensities and increases mean PSD-95:GFP fluorescence (Figures 3 and 5) are in general agreement with the aforementioned studies (see also [77],[82]).

Positive_regulation (increases) of PSD-95

7) Confidence 0.40 Published 2009 Journal PLoS Biology Section Body Doc Link PMC2693930 Disease Relevance 0 Pain Relevance 0.05

Fluoxetine produced a small but significant increase in hippocampal PSD-95 in ovariectomized wildtype mice but not in ovariectomized TrkB.T1 mice or sham mice.

Positive_regulation (increase) of PSD-95 associated with fluoxetine

8) Confidence 0.35 Published 2009 Journal Psychoneuroendocrinology Section Abstract Doc Link 18977602 Disease Relevance 0.10 Pain Relevance 0.87

Specifically, GABA-A alpha1 subunit, GRIA1 subunit and PSD-95 mRNAs were decreased in the shell but increased in the core following morphine administration.

Positive_regulation (increased) of PSD-95 in shell associated with gaba and morphine

9) Confidence 0.33 Published 2004 Journal Neuroscience Section Abstract Doc Link 15183518 Disease Relevance 0.09 Pain Relevance 1.22

In the core, neuronal apoptotic inhibitory protein (NAIP), GABA-A alpha1 subunit, GRIN2C, GRIA1, mGluR1, D4 dopamine receptor and PSD-95 were upregulated by morphine administration whereas bax, bcl-x, cox-1 and MAP2 were decreased.

Positive_regulation (upregulated) of PSD-95 in neuronal associated with gaba, dopamine receptor, apoptosis and morphine

10) Confidence 0.33 Published 2004 Journal Neuroscience Section Abstract Doc Link 15183518 Disease Relevance 0.10 Pain Relevance 1.31

When compared with a baseline reflex activity with a single action potential evoked by the TS before the administration of test agents, MO instillation into the descending colon sensitized the evoked activity characterized by elongated firing in the reflex activity in association with increased protein levels of Cdk5, PSD95, and phosphorylated NR2B (pNR2B) but not of total NR2B (tNR2B) in the spinal cord tissue.

Positive_regulation (increased) of PSD95 in descending colon associated with action potential and spinal cord

11) Confidence 0.29 Published 2009 Journal Pain Section Abstract Doc Link 19167822 Disease Relevance 0.23 Pain Relevance 0.45

Comparison of gene expression between the shell and core subregions of vehicle-treated rats revealed significantly higher relative abundance of GABA-A alpha1, Galphai2 and post-synaptic density protein 95 transcript (PSD-95) mRNA levels in the shell, whereas Ggamma2 and synuclein 1 were more abundant in the core of the NAc.

Positive_regulation (abundance) of PSD-95 in shell associated with nucleus accumbens and gaba

12) Confidence 0.24 Published 2004 Journal Neuroscience Section Abstract Doc Link 15183518 Disease Relevance 0.06 Pain Relevance 0.96

Our previous work has shown that PSD-95/SAP90 is required for NMDA receptor-mediated thermal hyperalgesia.

Positive_regulation (required) of SAP90 associated with thermal hyperalgesia and nmda receptor

13) Confidence 0.22 Published 2001 Journal Neuroreport Section Abstract Doc Link 11711866 Disease Relevance 0.70 Pain Relevance 0.62

CONCLUSION: The results indicate not only a significant decrease in MAC for isoflurane but also an attenuation in the NMDA-induced increase in isoflurane MAC in the PSD-95/SAP90 antisense-treated animals, which suggests that PSD-95/SAP90 may mediate the role of the NMDA receptor in determining the MAC of inhalational anesthetics.

Positive_regulation (increase) of SAP90

14) Confidence 0.22 Published 2001 Journal Anesthesiology Section Body Doc Link 11465592 Disease Relevance 0 Pain Relevance 0

Expression of behavioral sensitization in RHA-I rats activated secretogranin and PSD-95 mRNA in the nucleus accumbens core.

Positive_regulation (activated) of PSD-95 mRNA in nucleus accumbens associated with nucleus accumbens

15) Confidence 0.18 Published 2008 Journal Neuroscience Section Abstract Doc Link 18093743 Disease Relevance 0.07 Pain Relevance 0.18

The interactions with these synaptogenic factors suggest a potential role of PSD-95 and CASK in synapse formation.

Positive_regulation (role) of PSD-95 in synapse

16) Confidence 0.09 Published 2008 Journal The Journal of Cell Biology Section Body Doc Link PMC2447900 Disease Relevance 0.07 Pain Relevance 0

Ca2+ acts as a cosignal with PSD-95, a postsynaptic density protein for activation of neuronal NOS and thus couples NMDA receptor activation to NO, which, in excess, is toxic to RGCs [149].

Positive_regulation (activation) of PSD-95 in neuronal associated with nmda receptor

17) Confidence 0.03 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2647152 Disease Relevance 0.80 Pain Relevance 0.38

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