INT48853

Context Info Confidence 0.69 First Reported 1994 Last Reported 2010 Negated 2 Speculated 0 Reported most in Body Documents 82 Total Number 84 Disease Relevance 43.92 Pain Relevance 27.99

extracellular region (BDNF) cytoplasmic membrane-bounded vesicle (BDNF)

Anatomy Link Frequency brain 18 hippocampus 5 ciliary 4 nerve 3 neurons 3 BDNF (Homo sapiens)

Pain Link Frequency Relevance Heat Nerve growth factor 376 100.00 bDMF 28 100.00 medulla 19 100.00 antidepressant 429 99.90 excitatory amino acid 1 99.76 Glutamate 50 99.62 long-term potentiation 36 99.60 Central nervous system 82 99.54 Inflammation 223 99.50 Hippocampus 278 99.40

Disease Link Frequency Relevance Heat Apoptosis 176 100.00 Disease 817 99.96 Injury 167 99.96 Erythema 1 99.92 Diabetes Mellitus 194 99.84 Stress 741 99.76 Aids-related Complex 35 99.72 Neurodegenerative Disease 262 99.64 Rheumatoid Arthritis 62 99.52 INFLAMMATION 260 99.50

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

On the other hand, the increase in total BDNF mRNA after 48 hours of treatment appeared to be mainly accounted for by the induction of BDNF IV by both drugs.

Positive_regulation (induction) of BDNF IV

1) Confidence 0.69 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2483719 Disease Relevance 0.16 Pain Relevance 0.48

ProNGF levels were also found to be enhanced after CNS injury, together with upregulation of the p75 neurotrophin receptor and increased p75-mediated apoptosis [91].

Positive_regulation (upregulation) of neurotrophin associated with injury, central nervous system and apoptosis

2) Confidence 0.67 Published 2006 Journal BMC Neurosci Section Body Doc Link PMC1775042 Disease Relevance 1.38 Pain Relevance 0.18

that RA effects may involve an upregulation of neurotrophin receptors, and

Positive_regulation (upregulation) of neurotrophin associated with rheumatoid arthritis

3) Confidence 0.67 Published 2007 Journal PPAR Research Section Body Doc Link PMC1950239 Disease Relevance 0.95 Pain Relevance 0.19

The same research group, using the two-way active-avoidance learning paradigm, showed that the increase in pontine-wave density during post-training REM sleep is positively correlated with the increased levels of phosphorylated cAMP response element-binding protein (CREB), brain-derived nerve growth factor (BDNF), and Arc protein in the dorsal hippocampus (Ulloor and Datta, 2005).

Positive_regulation (increased) of BDNF in hippocampus associated with nerve growth factor, aids-related complex and hippocampus

4) Confidence 0.67 Published 2007 Journal Frontiers in Neuroscience Section Body Doc Link PMC2577304 Disease Relevance 0.23 Pain Relevance 0.10

Whether both NGF and BDNF are upregulated in the degenerate IVD, and as such play a key role in innervation and the pathogenesis of low back pain, however, remains to be determined.

Positive_regulation (upregulated) of BDNF associated with low back pain, nerve growth factor and backache

5) Confidence 0.65 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2575613 Disease Relevance 0.21 Pain Relevance 0.45

Recent animal and human studies have demonstrated that antidepressants can increase central as well as plasma BDNF levels.

Positive_regulation (increase) of BDNF in plasma associated with antidepressant

6) Confidence 0.61 Published 2005 Journal Med. Hypotheses Section Abstract Doc Link 15905042 Disease Relevance 0.91 Pain Relevance 1.31

Plasma BDNF was increased in the circulation in patients with unstable angina.

Positive_regulation (increased) of BDNF in Plasma associated with angina

7) Confidence 0.61 Published 2009 Journal Ann Cardiol Angeiol (Paris) Section Abstract Doc Link 19281964 Disease Relevance 0.52 Pain Relevance 0.14

On the other hand, the increase in total BDNF mRNA after 48 hours of treatment appeared to be mainly accounted for by the induction of BDNF IV by both drugs.

Positive_regulation (increase) of BDNF mRNA

8) Confidence 0.61 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2483719 Disease Relevance 0.15 Pain Relevance 0.49

In concert with this protection, there is an upregulation of neurotrophins [i.e., nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)].

Positive_regulation (upregulation) of BDNF in brain associated with nerve growth factor

9) Confidence 0.60 Published 2008 Journal J. Alzheimers Dis. Section Abstract Doc Link 18997293 Disease Relevance 0.36 Pain Relevance 0.40

In concert with this protection, there is an upregulation of neurotrophins [i.e., nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)].

Positive_regulation (upregulation) of brain-derived neurotrophic factor in brain associated with nerve growth factor

10) Confidence 0.60 Published 2008 Journal J. Alzheimers Dis. Section Abstract Doc Link 18997293 Disease Relevance 0.36 Pain Relevance 0.40

Increased levels of BDNF are necessary for the survival of neurons.

Positive_regulation (Increased) of BDNF in neurons associated with bdmf

11) Confidence 0.59 Published 2008 Journal Genome Biol Section Body Doc Link PMC2760875 Disease Relevance 0.65 Pain Relevance 0.52

Studies by Kemi and colleagues have demonstrated upregulation of NGF and BDNF in bronchial smooth muscle cells after treatment with IL-1 [26].

Positive_regulation (upregulation) of BDNF in smooth muscle cells associated with nerve growth factor

12) Confidence 0.57 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2575613 Disease Relevance 0.40 Pain Relevance 0.47

Similarly, in the brain, the mature form consisted in 60% of total BDNF and the proBDNF in 40% of total BDNF (Fig. 9B). 30 min of acute stress had no effects on the total amount of BDNF in the brain but induced a highly significant increase in the proBDNF levels and a corresponding significant reduction in mature BDNF (p < 0.01 vs. control, Fig. 9B).

Positive_regulation (increase) of proBDNF in brain associated with stress

13) Confidence 0.54 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2829032 Disease Relevance 0.10 Pain Relevance 0

Western blot analysis showed that in brain, but not in liver, proBDNF content is significantly increased in the stressed samples.

Positive_regulation (increased) of proBDNF in liver

14) Confidence 0.54 Published 2010 Journal BMC Neurosci Section Body Doc Link PMC2829032 Disease Relevance 0.50 Pain Relevance 0

It is well known that several intracellular pathways can mediate ERK phosphorylation in response to neurotrophins or other extracellular signals [47,48].

Positive_regulation (response) of neurotrophin

15) Confidence 0.49 Published 2006 Journal PLoS Pathogens Section Body Doc Link PMC1401496 Disease Relevance 0.54 Pain Relevance 0.43

Short-term treatment (6 hours) with reboxetine or desipramine reduced total BDNF, whereas long-term treatment (48 hours) significantly increased total BDNF mRNA levels.

Positive_regulation (increased) of BDNF mRNA associated with desipramine

16) Confidence 0.47 Published 2008 Journal BMC Neurosci Section Abstract Doc Link PMC2483719 Disease Relevance 0.16 Pain Relevance 0.50

Two way ANOVA showed significant effects of time (F2,144 = 37,42; p < .0001), drug (F2,144 = 23,39; p < .0001) and time/drug interaction (F4,144 = 26,94; p < .0001) for BDNF IV transcript: BDNF IV was significantly reduced after 6 hours and significantly increased after 48 h of RBX or DMI (Fig. 2B).

Positive_regulation (increased) of BDNF IV associated with desipramine

17) Confidence 0.47 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2483719 Disease Relevance 0 Pain Relevance 0.47

In addition, early social enrichment (offspring benefiting from the sharing of maternal care-giving by multiple females in a single nest) increases the brain's neurotrophin levels in young animals and shapes social competencies in adulthood[7].

Positive_regulation (increases) of neurotrophin in brain

18) Confidence 0.45 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2714966 Disease Relevance 0.09 Pain Relevance 0.13

In rodent studies, mouse pups receiving high levels of maternal care show increased neurotrophin levels in the brain, which promotes sociability in adulthood[7].

Positive_regulation (increased) of neurotrophin in brain

19) Confidence 0.45 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2714966 Disease Relevance 0.12 Pain Relevance 0.10

Therefore, tianeptine’s effectiveness as antidepressant treatment may result from its stabilization of neurotrophin levels in the amygdala.

Positive_regulation (stabilization) of neurotrophin in amygdala associated with antidepressant and amygdala

20) Confidence 0.45 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2701287 Disease Relevance 0.91 Pain Relevance 0.55

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