Unique Regulation of Immediate Early Gene and Tyrosine Hydroxylase Expression in the Odor-deprived Mouse Olfactory Bulb

Nian Liu,Elena Cigola,Cristina Tinti,Byung Kwan Jin,Bruno Conti,Bruce T Volpe,Harriet Baker

doi:10.1074/jbc.274.5.3042

Abstract

Tyrosine hydroxylase (TH), expressed in a population of periglomerular neurons intrinsic to the olfactory bulb, displays dramatic down-regulation in response to odor deprivation. To begin to elucidate the importance of immediate early genes (IEG) in TH gene regulation, the present study examined expression of IEGs in the olfactory bulb in response to odor deprivation. In addition, the composition of TH AP-1 and CRE binding complexes was investigated in control and odor-deprived mice. Immunocytochemical studies showed that c-Fos, Fos-B, Jun-D, CRE-binding protein (CREB), and phosphorylated CREB (pCREB) are colocalized with TH in the dopaminergic periglomerular neurons. Unilateral naris closure resulted in down-regulation of c-Fos and Fos-B, but not Jun-D, CREB, or pCREB, in the glomerular layer of the ipsilateral olfactory bulb. Gel shift assays demonstrated a significant decrease (32%) in TH AP-1, but not CRE, binding activity in the odor-deprived bulb. Fos-B was found to be the exclusive member of the Fos family present in the TH AP-1 complex. CREB, CRE modulator protein (CREM), Fos-B, and Jun-D, but not c-Fos, all contributed to the CRE DNA-protein complex. These results indicated that Fos-B, acting through both AP-1 and CRE motifs, may be implicated in the regulation of TH expression in the olfactory bulb dopaminergic neurons.

Highlights

Immediate early genes (IEGs)1 encode transcription factors that are induced rapidly by extracellular signals and regulate expression of target genes
Tissue Localization and Regulation of Tyrosine hydroxylase (TH) and IEGs—As previously shown [38], in the control olfactory bulb TH was concentrated in cell bodies and processes of periglomerular neurons located in the glomerular layer of olfactory bulb (Fig. 1A)
TH AP-1 and CRE Binding Activities—Because naris closure produced down-regulation in expression of some IEG products in parallel to that observed for TH in periglomerular neurons, gel retardation assays were performed to determine whether TH AP-1 and CRE binding activities in olfactory bulb were altered by odor deprivation

Summary

Introduction

Immediate early genes (IEGs)1 encode transcription factors that are induced rapidly by extracellular signals and regulate expression of target genes. To elucidate some of the cis- and trans-acting elements important in regulating TH expression in the olfactory bulb periglomerular neurons, the current studies employed immunocytochemical, Western blot, and gel shift analyses to investigate the composition of the AP-1 and CRE binding complexes.

Results

Conclusion