Complex catecholaminergic modulation of the stimulatory effect of interleukin-1 beta on the corticotropic axis.
ABSTRACT We recently showed that bilateral neurotoxic microlesions (6-OH-DA) of the ventral noradrenergic ascending bundle (VNAB-X) at stereotaxic coordinates that blocked corticotropic stress responses did not affect the ACTH surge after bilateral intra-paraventricular (i.PVN) injections of interleukin-1 beta (IL-1 beta), and that lesioning at these stereotaxic coordinates obliterated the dorsal axonal populations of the VNAB (dVNAB-X), but spared the bundle's most ventral axons (vVNAB). The present study compares the effects of IL-1 beta given i.PVN (2 x 5 ng) of intra-arterially (i.a.) (100 ng) on plasma ACTH in rats with bilateral 6-OH-DA microlesions placed in the dVNAB or the vVNAB, or in an intermediary central position (cVNAB-X). Unlike our previous results, in which dVNAB-X did not alter the biphasic ACTH response to i.PVN IL-1 beta, both vVNAB-X and cVNAB-X reduced by 50-75% the early and delayed ACTH surges which are typical of the i.PVN route. On the other hand the swift monophasic ACTH surge usually occurring after an i.a. injection of IL-1 beta was 65% smaller after dVNAB-X, but was doubled after vVNAB-X or cVNAB-X. Hence, the release of ACTH after both i.PVN or i.a. IL-1 beta requires brainstem afferences conveyed to the hypothalamus by the VNAB. However, the VNAB appears to include at least two functionally different subsets of axons, the roles of which in the ACTH response to IL-1 beta depend on the route by which the cytokine is given.
- SourceAvailable from: Puliyur S Mohankumar[show abstract] [hide abstract]
ABSTRACT: Interleukin-1beta (IL-1beta), a cytokine with pronounced central effects such as fever, anorexia, analgesia, etc., is also known to activate the hypothalamo-pituitary-adrenal (HPA) axis. Corticotropin releasing hormone (CRH) neurons located in the hypothalamus are important for HPA activation. The cell bodies of CRH neurons are located in the paraventricular nucleus (PVN) and their terminals are present in the median eminence (ME). Although the catecholamines, norepinephrine (NE) and dopamine (DA) are believed to be crucial factors in the stimulation of CRH neurons, it is not clear if they affect the cell bodies or terminals of these neurons to cause HPA activation. This study was done to determine if IL-1beta affects NE and DA release at the level of CRH cell bodies or their terminals. Adult male Sprague-Dawley rats were implanted with two push-pull cannulae, one in the PVN and another in the ME, and were subjected to push-pull perfusion. They were treated either with 0, 1 or 5 microg of IL-1beta. Perfusates were collected for 2 h after treatment and analyzed for NE concentrations using HPLC-EC. NE levels in the control and low dose groups did not change significantly during the entire period of observation both in the PVN and ME. In contrast, treatment with 5 microg of IL-1beta produced a marked increase in NE release in the PVN at 20 and 40 min post-treatment. NE release in the ME increased from 10 to 140 min post-treatment. There were no significant changes in the release of DA from both these areas. These results indicate that IL-1beta increases NE levels both in the PVN and in the ME and this could be a possible mechanism by which it stimulates the HPA axis.Brain Research Bulletin 06/2005; 65(5):451-6. · 2.94 Impact Factor
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ABSTRACT: Neurotoxicity induced by hydroxyl radicals (OH) release is thought to be involved in a number of acute and chronical neuropathologies of the central nervous system. As far as neurodegenerative processes are concerned, the possible mechanisms giving rise to such OH releases remain poorly understood. In the present study, unanesthetized rats were perfused with a low salicylate solution through a chronic microdialysis cannula implanted into the striatum, and the OH responses to glutamate were analyzed. A single bolus of 3 mM glutamate elicited only minute releases of OH in naive rats. By contrast, recurrent infusions at 1-week intervals of the same glutamate concentration induced a robust OH response. Similar potentiation of the initial response also occurred for a larger glutamate concentration (30 mM). Oppositely, multiple injections of a high (300 mM) glutamate concentration resulted in a slow down of the initial OH response recorded in naive animals. The mechanisms giving rise to such effects are presently unknown. It is, however, clear that repetitive dysfunctions of the glutamate neurotransmission may be sufficient to promote the release of significant amounts of hydroxyl radicals, resulting in a progressive impairment of the astrocytic glutamate transporter, leading to neurodegenerative processes.Journal of Neuroscience Research 05/1999; 56(2):160-5. · 2.97 Impact Factor
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ABSTRACT: We have investigated whether the serotonin system participates in the mechanisms underlying the corticotropic response in experimentally infected rats. Intra-arterial injection of lipopolysaccharide (LPS; 25 microg/kg b.w.) resulted in a slight but significant increase in serotonin (5-HT) metabolism, detectable 60 min after the stimulus and lasting more than 480 min. Adrenocorticotropin (ACTH) and corticosterone (CORT) responses in intact rats conformed to earlier reports, increasing as early as 30 min after LPS injection and reaching maximal concentrations in the circulation 60 min after the bacterial endotoxin injection. Plasma concentrations of interleukin-1beta (IL-1beta) increased only after 60 min, reaching maximal levels 120 min after LPS. Depletion of hypothalamic 5-HT (-93%) by pretreatment of the animals with para-chlorophenylalanine (p-CPA), resulted in a halved ACTH response to LPS, despite an overall unchanged secretory pattern. Neither CORT nor IL-1beta secretory patterns were affected in these rats pretreated with p-CPA. Complete bilateral electrochemical lesions of the suprachiasmatic nucleus (SCN), which is innervated by mesencephalic 5-HT, impaired the early phase of the ACTH (-75% at 30 min) and CORT (-40% at 30 min) responses but did not affect the later increases of the corticotropic and the plasma IL-1beta responses following the LPS injection. These results indicate that serotonin pathways and SCN are involved in the earlier mechanisms of corticotropic axis recruitment following systemic LPS endotoxemia.Journal of Neuroendocrinology 09/1999; 11(8):629-36. · 3.33 Impact Factor