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Induction of transcription factor AP2 mRNA expression in rat primary afferent neurons during acute inflammation
L F Donaldson1, D S McQueen, J R Seckl
1Department of Medicine, Western General Hospital, University of Edinburgh, UK.
Abstract:
We have examined immediate early gene mRNA expression, using in situ hybridisation in innervating dorsal root ganglion (DRG) neurons following peripheral adjuvant injection. Neuronal expression of mRNAs encoding NGFI-A (nerve growth factor-induced), NGFI-B, c-jun, jun D and jun B was undetectable in untreated controls and was unchanged following adjuvant injection. AP-2 mRNA was expressed in the majority of DRG neurons in untreated controls and was significantly increased (217 +/- 43% control) 1 h after adjuvant injection. AP2 mRNA levels returned to control values by 2 h post-injection. AP-2 may form part of the early transcriptional response that induces neuropeptide gene expression in DRG after adjuvant injection.
Insights
Peripheral adjuvant injection increased AP-2 mRNA expression in dorsal root ganglion (DRG) neurons. This early gene response may trigger neuropeptide gene expression in DRG following injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Peripheral nerve injury and inflammation trigger complex cellular responses in sensory neurons.
- Immediate early genes (IEGs) are rapidly activated following cellular stimulation and play a role in long-term changes in gene expression.
- Dorsal root ganglion (DRG) neurons are primary sensory neurons involved in transmitting pain and other sensory information.
Purpose of the Study:
- To investigate the expression of immediate early gene mRNAs in DRG neurons after peripheral adjuvant injection.
- To identify specific IEGs involved in the early transcriptional response to peripheral inflammation.
- To explore the potential role of AP-2 transcription factor in initiating neuropeptide gene expression in DRG neurons.
Main Methods:
- In situ hybridization was used to examine mRNA expression in DRG neurons.
- Peripheral adjuvant injection was administered to induce an inflammatory response.
- Expression levels of several IEGs, including NGFI-A, NGFI-B, c-jun, jun D, jun B, and AP-2, were quantified.
Main Results:
- Neuronal expression of NGFI-A, NGFI-B, c-jun, jun D, and jun B mRNAs was undetectable or unchanged after adjuvant injection.
- AP-2 mRNA was expressed in most DRG neurons in control conditions.
- AP-2 mRNA levels significantly increased 1 hour after adjuvant injection (217% of control) and returned to baseline by 2 hours.
Conclusions:
- AP-2 mRNA expression is rapidly and transiently upregulated in DRG neurons following peripheral adjuvant injection.
- AP-2 may be a key component of the early transcriptional response that leads to neuropeptide gene expression in DRG neurons.
- This study identifies AP-2 as a potential early marker and mediator in the neuroinflammatory response within the DRG.