PMID- 17488277
OWN - NLM
STAT- MEDLINE
DCOM- 20071004
LR  - 20200714
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 102
IP  - 4
DP  - 2007 Aug
TI  - Neurotrophin activation of NFAT-dependent transcription contributes to the 
      regulation of pro-nociceptive genes.
PG  - 1162-74
AB  - Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) play key 
      roles in the development of inflammation-induced hyperalgesia by triggering the 
      expression of pro-nociceptive genes within primary afferent and spinal neurons. 
      However, the mechanisms by which neurotrophins elicit gene expression remain 
      largely unknown. Recently, neurotrophins have been shown to activate members of 
      the calcineurin (CaN)-regulated, nuclear factor of activated T-cells (NFATc) 
      family of transcription factors within brain. Thus, we hypothesized that NFATc 
      transcription factors couple neurotrophin signaling to gene expression within 
      primary afferent and spinal neurons. In situ hybridization revealed NFATc4 mRNA 
      within the dorsal root ganglion and spinal cord. In cultured dorsal root ganglion 
      cells, NGF triggered NFAT-dependent transcription in a CaN-sensitive manner. 
      Further, increased BDNF expression following NGF treatment relied on CaN, thereby 
      suggesting that NGF regulates BDNF transcription via activation of NFATc4. Within 
      cultured spinal cells, BDNF also activated CaN-dependent, NFAT-regulated gene 
      expression. Interestingly, BDNF stimulation increased the expression of the 
      pro-nociceptive genes cyclooxygenase-2, neurokinin-1 receptor, inositol 
      trisphosphates receptor type 1, and BDNF itself, through both NFAT-dependent and 
      NFAT-independent transcriptional mechanisms. Our results suggest that regulation 
      of pro-nociceptive genes through activation of NFAT-dependent transcription is 
      one mechanism by which NGF and BDNF signaling contributes to the development of 
      persistent pain states.
FAU - Groth, Rachel D
AU  - Groth RD
AD  - Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 
      55455, USA.
FAU - Coicou, Lia G
AU  - Coicou LG
FAU - Mermelstein, Paul G
AU  - Mermelstein PG
FAU - Seybold, Virginia S
AU  - Seybold VS
LA  - eng
GR  - DA017881/DA/NIDA NIH HHS/United States
GR  - DA07234/DA/NIDA NIH HHS/United States
GR  - NS48286/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Nerve Growth Factors)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 3.1.3.16 (Calcineurin)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Calcineurin/genetics/*metabolism
MH  - Cells, Cultured
MH  - Drug Interactions
MH  - Female
MH  - Ganglia, Spinal/cytology
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - In Situ Hybridization/methods
MH  - Mice
MH  - Mice, Inbred C3H
MH  - NFATC Transcription Factors/genetics/*metabolism/pharmacology
MH  - Nerve Growth Factor/metabolism/pharmacology
MH  - Nerve Growth Factors/*metabolism/physiology
MH  - Neurons/drug effects/metabolism
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tacrolimus/pharmacology
MH  - Transcription, Genetic/drug effects/*physiology
EDAT- 2007/05/10 09:00
MHDA- 2007/10/05 09:00
CRDT- 2007/05/10 09:00
PHST- 2007/05/10 09:00 [pubmed]
PHST- 2007/10/05 09:00 [medline]
PHST- 2007/05/10 09:00 [entrez]
AID - JNC4632 [pii]
AID - 10.1111/j.1471-4159.2007.04632.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Aug;102(4):1162-74. doi: 10.1111/j.1471-4159.2007.04632.x.