INT198743

Context Info Confidence 0.37 First Reported 2006 Last Reported 2010 Negated 2 Speculated 1 Reported most in Body Documents 11 Total Number 14 Disease Relevance 1.34 Pain Relevance 1.50

plasma membrane (Psd) intracellular (Psd) cytoplasm (Psd)

Anatomy Link Frequency synapses 4 spine 2 chromaffin cells 1 cerebellum 1 Psd (Mus musculus)

Pain Link Frequency Relevance Heat Catecholamine 30 99.76 nMDA receptor 40 99.56 Hippocampus 37 93.24 imagery 158 90.08 GABAergic 29 81.92 long-term potentiation 159 81.48 Spinal cord 1 73.20 Neurobehavioral 18 71.60 medulla 2 68.48 Glutamate receptor 40 39.96

Disease Link Frequency Relevance Heat Targeted Disruption 37 100.00 Adhesions 17 93.76 Pheochromocytoma 48 86.72 Convulsion 3 67.84 Syndrome 45 64.80 Congenital Anomalies 3 64.16 Respiratory Failure 1 63.88 Autism 9 50.00 Body Weight 12 43.80 Generalized Anxiety Disorder 2 43.12

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

2 in the adult cerebellum induces a parallel expansion of the PSD and a reduction of the presynaptic active zone, suggesting that GluR?

Gene_expression (expansion) of PSD in cerebellum

1) Confidence 0.37 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2666267 Disease Relevance 0.25 Pain Relevance 0

Significant changes in protein levels of NMDA receptor subunits NR1 and NR2A, and NMDA receptor interacting proteins PSD-95 and SAP97 were not detected.

Neg (not) Gene_expression (detected) of PSD associated with nmda receptor

2) Confidence 0.36 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1892123 Disease Relevance 0 Pain Relevance 0.38

We next studied the relationship between PSD size and the PSD's retention time for PSD-95-paGFP*.

Gene_expression (size) of PSD

3) Confidence 0.35 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1634879 Disease Relevance 0 Pain Relevance 0.04

Without synapse-specific regulation of kinetic parameters, the interactions between PSD molecules and PSDs are identical in all spines; large PSDs would therefore lose material and size at the expense of small PSDs, until all PSDs have a similar size.

Gene_expression (molecules) of PSD in synapse

4) Confidence 0.35 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1634879 Disease Relevance 0 Pain Relevance 0.04

These observations argue that PSD-95 spreads from PSD to PSD by diffusion and individual PSDs share a common pool of diffusing PSD-95.

Gene_expression (spreads) of PSD

5) Confidence 0.35 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1634879 Disease Relevance 0 Pain Relevance 0.05

Significant changes in protein levels of NMDA receptor subunits NR1 and NR2A, and NMDA receptor interacting proteins PSD-95 and SAP97 were not detected.

Neg (not) Gene_expression (detected) of PSD associated with nmda receptor

6) Confidence 0.32 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1892123 Disease Relevance 0 Pain Relevance 0.38

Moreover, there was no expression of full-length Shank3 protein in PSD fractions from Shank3-knockout mice and reduced expression in the heterozygotes, using antibodies which cross-react either with an epitope downstream of the PDZ domain (antibody N69/46; see Figure 1A) (Figure 1C) or with the COOH terminal (data not shown), consistent with haploinsufficiency.

Gene_expression (expression) of PSD associated with targeted disruption

7) Confidence 0.31 Published 2010 Journal Mol Autism Section Body Doc Link PMC3019144 Disease Relevance 0.32 Pain Relevance 0

Our measurements suggest that kinetic mechanisms tuned at the level of individual synapses could help maintain PSD size with dynamic PSD components.

Gene_expression (size) of PSD in synapses

8) Confidence 0.31 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1634879 Disease Relevance 0 Pain Relevance 0.07

How can PSD size be maintained in the presence of diffusion?

Gene_expression (size) of PSD

9) Confidence 0.31 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1634879 Disease Relevance 0 Pain Relevance 0.03

Our measurements suggest that kinetic mechanisms tuned at the level of individual synapses could help maintain PSD size with dynamic PSD components.

Gene_expression (size) of PSD in synapses

10) Confidence 0.31 Published 2006 Journal PLoS Biology Section Body Doc Link PMC1634879 Disease Relevance 0 Pain Relevance 0.07

Additional studies showed that knockout of Shank1 leads to a decrease in spine number and spine and PSD size, decreased levels of GKAP and Homer, and reduced basal synaptic transmission [18].

Gene_expression (size) of PSD in spine associated with targeted disruption

11) Confidence 0.30 Published 2010 Journal Mol Autism Section Body Doc Link PMC3019144 Disease Relevance 0.28 Pain Relevance 0

Additional studies showed that knockout of Shank1 leads to a decrease in spine number and spine and PSD size, decreased levels of GKAP and Homer, and reduced basal synaptic transmission [18].

Gene_expression (levels) of PSD in spine associated with targeted disruption

12) Confidence 0.30 Published 2010 Journal Mol Autism Section Body Doc Link PMC3019144 Disease Relevance 0.28 Pain Relevance 0

In additional ex vivo experiments, we investigated protein expression levels in the postsynaptic density (PSD) and catecholamine release from chromaffin cells to further reveal underlying mechanisms.

Spec (investigated) Gene_expression (expression) of PSD in chromaffin cells associated with catecholamine

13) Confidence 0.27 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1892123 Disease Relevance 0.09 Pain Relevance 0.28

The expression level of PSD 95 seems to influence the relative amounts of excitatory and inhibitory synapses and therefore critically affects the E/I balance (for details see Keith and El-Husseini in this issue) (Liu, 2004).

Gene_expression (expression) of PSD in synapses

14) Confidence 0.18 Published 2008 Journal Frontiers in Molecular Neuroscience Section Body Doc Link PMC2526003 Disease Relevance 0.12 Pain Relevance 0.18

General Comments

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