Systemic immune challenge induces preproenkephalin gene transcription in distinct autonomic structures of the rat brain

Abstract

The involvement of enkephalins in the immune response was investigated in rats injected intravenously with interleukin-1beta (2 microg/kg). In situ hybridization with a riboprobe complementary to intron A of the preproenkephalin (ppENK) gene showed distinct transcriptional activation within several brain regions known to be activated by immune stimuli, including the nucleus of the solitary tract, the area postrema, the paraventricular hypothalamic nucleus, and the oval nucleus of the bed nucleus of the stria terminalis, and dual labeling confirmed that a large proportion of the intron expressing neurons co-expressed c-fos mRNA. Rats injected with saline (controls) showed little or no heteronuclear transcript in these structures. The induced signal was strongest after 1 hour but was present in some structures 30 minutes after interleukin-1beta injection. At 3 hours, transcriptional activity returned to basal levels. High basal expression of the heteronuclear transcript that appeared unchanged by the immune stimulus was seen in regions not primarily involved in the immune response, such as the striatum, the olfactory tubercle, and the islands of Calleja and in the immune activated central nucleus of the amygdala. The heteronuclear transcript colocalized with ppENK mRNA, demonstrating that it occurred in enkephalinergic neurons and was not the result of alternative transcription from the ppENK gene in other cells. These results demonstrated that enkephalin transcription is induced in central autonomic neurons during immune challenge, suggesting that enkephalins are involved in the centrally orchestrated response to such stimuli.

Allopregnanolone and suppressed hypothalamo–pituitary–adrenal axis stress responses in late pregnancy in the rat

“…Moreover, AP treatment up-regulates pENK-A mRNA expression in brainstem NTS neurons of virgin rats by 35% (Brunton et al 2009), which is comparable with the 31% increase reported in late pregnancy . Induction of inhibitory opioid tone over HPA axis responses to IL-1b by AP treatment occurs within 20 h, consistent with the rapid increase in pENK-A mRNA expression in the NTS that has been seen after IL-1b treatment (Engstrom et al 2003). Clearly, our model presumes that increased NTS pENK-A mRNA expression leads to synthesis and rapid axonal transport to the pPVN of ENK; this remains to be tested.…”

Neurosteroids and GABA-A Receptor Function

“…Allopregnanolone induces opioid tone (as revealed by naloxone treatment) over ACTH responses to immune challenge in virgin rats (Brunton et al, 2009). Induction of inhibitory opioid tone over HPA axis responses to IL-1β by AP treatment occurs within 20 h, consistent with the rapid increase in pENK-A mRNA expression in the NTS that has been seen after IL-1β treatment (Engstrom et al, 2003). The mechanism by which AP upregulates opioid expression in the NTS is not clear.…”

The transcriptome of the medullary area postrema: the thirsty rat, the hungry rat and the hypertensive rat

“…Although some of these ion channel isoformsn, such as HCN, have previously been identified in AP (Milligan et al 2006), this is the first comprehensive description of the ion channels expressed in AP. The literature also validates several key signalling molecules involved in water and energy homeostasis that have been identified in the AP at either the protein or the transcript level, such as angiotensinogen (Agt; Lewicki et al 1978), apelin (Apln; Reaux et al 2002), proenkephalin (Penk1; Rutherfurd & Gundlach, 1993;Engstrom et al 2003), thyrotrophin-releasing hormone (Trh; Iwase et al 1988), calcitonin/calcitonin-related polypeptide α (Calca; Fodor et al 1994), cocaine and amphetamine related transcript (Cartpt; Zheng et al 2002) and galanin (Gal; Krukoff et al 1992;Koegler & Ritter, 1998;Fig. 2).…”