Biomedical subjects

W Rowe

Publications and source records attributed to W Rowe.

At least 19 recordsLinked to original sources

PubMed2005

The ability of fruit teas to remove the smear layer: an in vitro study of tubule patency.

OBJECTIVES: Fruit teas are know to have an erosive effect on enamel, but the effects on dentine are unknown. Lesions of dentine hypersensitivity have numerous patent dentinal tubules and the aim of this paper was to examine the ability of various fruit teas to remove the smear layer. METHODS: The erosive potential of a variety of fruit teas was assessed in the laboratory by measuring their pH and neutralisable acidity. Smeared dentine specimens were prepared from extracted teeth and the ability of each tea to remove the smear layer was assessed by measuring the diameter and area of the opened tubules and counting the number of patent tubules seen in a unit area using scanning electron microscopy. A 0.2% citric acid solution was used as a positive control. RESULTS: The pH of the fruit teas ranged from 2.98 to 3.95 and the neutralisable acidity ranged from 10.63 to 33.0 ml of 0.1 M NaOH. All the fruit teas tested were able to remove the smear layer. The mean diameter of the tubules ranged from 0.61 to 1.14 microm and the mean area ranged from 0.31 to 1.03 microm2. The number of patent tubules per specimen ranged from 13 to 121. CONCLUSION: All the fruit teas tested were found to be highly acidic and able to remove the smear layer.

Dental Enamel↗

PubMed2001

Founding editorial--forensics and TheScientificWorld.

At the beginning of a new millennium it seems a good idea to stop for a moment and take stock of the current state of forensic science. As a field of scientific research and scientific application, forensic science is a little more than a century old. Forensic science may be said to have begun in 1887 with the simultaneous publication of A. Conan Doyle's A Study in Scarlet and Hans Gross's Handbuch f1/4r Untersuchungsrichter. Conan Doyle's novel introduced to the world the character of Sherlock Holmes, whose literary career would popularize the use of physical evidence in criminal investigations. Gross's manual for examining magistrates suggests ways in which the expertise of chemists, biologists, geologists, and other natural scientists could contribute to investigations. Gross's book was translated into a number of languages and went through various updated editions during the course of the century. The intervening century saw the development and application of fingerprinting, firearm and tool mark identification, forensic chemistry, forensic biology, forensic toxicology, forensic odontology, forensic pathology, and forensic engineering. Increasingly, the judicial systems of the industrial nations of the world have come to rely upon the expertise of scientists in a variety of disciplines. In most advanced countries, virtually all criminal prosecutions now involve the presentation of scientific testimony. This has had the beneficial effect of diminishing the reliance of courts on eyewitness testimony and defendant confessions.

DNA↗

PubMed2001

Amyloid beta peptide levels and its effects on hippocampal acetylcholine release in aged, cognitively-impaired and -unimpaired rats.

Excessive extracellular deposition of amyloid beta (Abeta) peptide in neuritic plaques and degeneration of forebrain cholinergic neurones, which innervate the hippocampus and the neocortex, are the invariant characteristic features of Alzheimer's disease (AD). Studies of the pathological changes that characterize AD, together with several other lines of evidence, indicate that Abeta accumulation in vivo may initiate and/or contribute to the process of neurodegeneration observed in the AD brain. However, the underlying mechanisms by which Abeta peptide influences/causes degeneration of the basal forebrain cholinergic neurones in AD brains remain obscure. We reported earlier that nM concentrations of Abeta-related peptides, under acute conditions, can potently inhibit K+-evoked endogenous acetylcholine (ACh) release from the hippocampus and the cortex but not from striatum in young adult rats (J. Neurosci. 16 (1996) 1034). In the present study, to determine whether the effects of Abeta peptides alter with normal aging and/or cognitive state, we have measured Abeta1-40 levels and the effects of exogenous Abeta1-40 on hippocampal ACh release in young adult as well as aged cognitively-unimpaired (AU) and -impaired (AI) rats. Endogenous levels of Abeta(1-40) in the hippocampus are significantly increased in aged rats. Additionally, 10 nM Abeta1-40 potently inhibited endogenous ACh release from the hippocampus of the three groups of rats, but the time-course of the effects clearly indicate that the cholinergic neurones of AI rats are more sensitive to Abeta peptides than either AU or young adult rats. These results, together with earlier reports, suggest that the processing of the precursor protein of Abeta peptide alters with normal aging and the response of the cholinergic neurones to the peptide possibly varies with the cognitive status of the animals.

Acetylcholine↗

PubMed2000

Increase in AMPA receptors in aged memory-impaired rats is not associated with increase in monoamine oxidase B levels.

Aged rats may be behaviorally classified as either cognitively impaired or unimpaired based upon their performance in the Morris water maze task. In aged Long-Evans rats, emergence of functional deficits has been related to the increase in the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subtype in most hippocampal subfields, not observed in other brain structures. As AMPA receptors expressed in astrocytes may participate in the delayed and long-term glial response to injury, we investigated whether astrocytes participate in the increase of AMPA receptor observed in these aged rats. To this end, distribution of monoamine oxidase B, used as an astroglial marker, was characterized by quantitative autoradiography in the hippocampus and septum of young adults (six months) and aged (24-25 months) rats using [3H]lazabemide. Specific binding to brain sections of young, aged unimpaired, and aged impaired animals were calculated densitometrically. Compared to young animals, all hippocampal subfields in the aged unimpaired group showed a significant age-related increased labeling, which was not present in the aged impaired group. This contrasts with the increased glial transcription described in this last group. We propose that increase in AMPA receptors in the aged memory-impaired animals may be related to an atypic astrocytic reactivity.

Aging↗

PubMed1997

Spatial memory in transgenic mice with impaired glucocorticoid receptor function.

Spatial learning and memory function of transgenic mice with impaired glucocorticoid receptor function was assessed in the Morris water maze and the radial arm maze. Transgenic mice took longer to find a submerged and a visual platform in the water maze task than did mice from the parent strain (B6C/3F1), although performance was improved in the visible platform condition relative to the submerged platform task. In the radial arm maze, transgenic mice made significantly more errors than B6C/3F1 mice. In both tasks, the behavioural strategies adopted by transgenic mice were non-optimal for correct performance. It is suggested that the impaired performance displayed by transgenic mice in both tests is largely attributable to these altered behavioural strategies.

Animals↗

PubMed1997

Neurotoxic consequences of central long-term administration of interleukin-2 in rats.

Interleukin-2 is an immunoregulatory cytokine with several recently established CNS activities. Central effects of interleukin-2 include growth promotion for neuronal and glial cells as well as modulatory influences on neurotransmission and hormone release. However, little is known about the consequences in the CNS of chronically elevated levels of interleukin-2. Alterations in the interleukin-2/interleukin-2 receptor system are not only associated with CNS trauma, inflammation and certain neuropathologies; elevated interleukin-2 concentrations are especially induced during the therapeutic use of interleukin-2 in cancer treatments. In the present study, intracerebroventricular (i.c.v.) interleukin-2 infusions (5 15 U/h) were performed in Sprague Dawley rats for up to 14 days. Interleukin-2-treated animals showed significantly increased plasma levels of corticosterone indicating an hyperfunctioning of the hypothalamic-pituitary-adrenocortical axis that lasted over the 14 day infusion period. Moreover, the performance of interleukin-2-treated animals in the Morris swim maze task was transiently impaired. Quantitative receptor autoradiographic analyses revealed changes in the binding levels of cholinergic M1 and M2 as well as dopaminergic D1 and D2 receptors in selected brain areas in which interleukin-2 was shown to modulate neurotransmission and which are enriched with interleukin-2 receptor expression. Decreased receptor binding levels were observed in the frontoparietal cortex (M2, D1, D2), hippocampal CA1 region (M1, M2) and the nucleus accumbens (D2). Histological and immunohistochemical examination of the brains of interleukin-2-treated animals revealed multiple alterations. Interleukin-2 treatment resulted in an intracranial accumulation of non-neural, MHC class II-positive cells as well as T and B lymphocytes within the infused brain hemisphere. Cellular infiltrates were associated with angiogenesis and the deposition of extracellular matrix material, such as fibronectin. Adjacent brain regions that were partly invaded and dislodged by the cellular masses were characterized by reactive astrogliosis, microglial activation, endothelial upregulation of adhesion molecules, myelin damage and neuronal loss. Together the data suggest that persistently elevated central levels of interleukin-2 can interfere with several CNS functions and may lead to nervous tissue injury. These findings could be relevant to CNS pathologies characterized by abnormal interleukin-2 production and to central responses to interleukin-2 treatments.

Animals↗

PubMed1997

Distribution and levels of [125I]IGF-I, [125I]IGF-II and [125I]insulin receptor binding sites in the hippocampus of aged memory-unimpaired and -impaired rats.

The insulin-like growth factors (IGF-I and IGF-II) and insulin are localized within distinct brain regions and their respective functions are mediated by specific membrane receptors. High densities of binding sites for these growth factors are discretely and differentially distributed throughout the brain, with prominent levels localized to the hippocampal formation. IGFs and insulin, in addition to their growth promoting actions, are considered to play important roles in the development and maintenance of normal cell functions throughout life. We compared the anatomical distribution and levels of IGF and insulin receptors in young (five month) and aged (25 month) memory-impaired and memory-unimpaired male Long Evans rats as determined in the Morris water maze task in order to determine if alterations in IGF and insulin activity may be related to the emergence of cognitive deficits in the aged memory-impaired rat. In the hippocampus, [125I]IGF-I receptors are concentrated primarily in the dentate gyrus (DG) and the CA3 sub-field while high amounts of [125I]IGF-II binding sites are localized to the pyramidal cell layer, and the granular cell layer of the DG. [125I]insulin binding sites are mostly found in the molecular layer of the DG and the CA1 sub-field. No significant differences were found in [125I]IGF-I. [125I]IGF-II or [125I]insulin binding levels in any regions or laminae of the hippocampus of young vs aged rats. and deficits in cognitive performance did not relate to altered levels of these receptors in aged memory-impaired vs aged memory-unimpaired rats. Other regions. including various cortical areas, were also examined and failed to reveal any significant differences between the three groups studied. It thus appears that IGF-I, IGF-II and insulin receptor sites are not markedly altered during the normal ageing process in the Long Evans rat, in spite of significant learning deficits in a sub-group (memory-impaired) of aged animals. Hence. recently reported changes in IGF-I receptor messenger RNA levels in aged memory-impaired rats are apparently not reflected at the level of the translated protein.

Aging↗

PubMed1997

Dynamic variations in plasma corticosteroid-binding globulin and basal HPA activity following acute stress in adult rats.

We report on dynamic changes in plasma corticosteroid-binding globulin (CBG) binding and basal hypothalamic-pituitary-adrenal (HPA) activity following acute stress in adult rats. Plasma CBG binding was significantly reduced at 24 and 48 h following a single 60 min period of restraint. Basal levels of plasma ACTH and total corticosterone (B) during the light phase of the cycle were elevated at 24 h following restraint. These effects occurred only when animals were stressed in the light phase of the cycle; animals exposed to restraint stress during the dark phase of the cycle showed no change in plasma CBG binding or in basal HPA activity. Pituitary intracellular transcortin, which is derived from circulating CBG, was also decreased by restraint stress. The decrease in CBG binding was also associated with a significant increase in resting-state free B levels. Together, these effects produced a substantially (i.e. approximately 10-fold) increased 'basal' glucocorticoid signal 24 h following acute stress. These data suggest that the increase in the circulating glucocorticoid signal associated with acute stress endures well beyond the period of increased total B levels.

Adrenal Glands↗

PubMed1996

Phasic hyperactivity of the HPA axis resulting from chronic central IL-2 administration.

Intracerebroventricular infusion of interleukin-2 (IL-2, 15 U h-1 for 14 days) chronically activated the hypothalamic-pituitary-adrenocortical (HPA) axis in rats. IL-2 induced increases in plasma levels of adrenocorticotropic hormone (ACTH, up to two-fold) and corticosterone (up to four-fold) compared with controls. Continuously elevated brain levels of IL-2 did not lead to a persistent HPA activation, but resulted in (two) periods of hormonal hypersecretion. ACTH and corticosterone levels were elevated between days 3 and 5, with changes in corticosterone preceding those of ACTH. Concentrations of corticosterone, but not of ACTH, increased again on day 11. Underscoring its importance as a neuroendocrine regulator, this study reveals that, in addition to its immediate effects, IL-2 induces a complex pattern of chronic HPA stimulation. These findings may functionally relate to several CNS disorders and certain endocrine dysfunctions observed during IL-2 immunotherapy.

Adrenocorticotropic Hormone↗

PubMed1996

Ionotropic glutamate receptor subtypes in the aged memory-impaired and unimpaired Long-Evans rat.

The comparative quantitative autoradiographic distribution of ionotropic glutamate receptor subtypes were investigated in young adults (six months) and aged (24-25 months) cognitively impaired and unimpaired male Long-Evans rats. Aged rats were behaviorally characterized as either cognitively impaired or unimpaired based upon their performances in the Morris water maze task compared to the young adult controls. The status of the N-methyl-D-aspartate, [125I]dizocilpine maleate, [3H]kainate and amino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA, [3H]AMPA) receptor binding sites were then established in these three subgroups of animals as a function of their cognitive performance in the Morris water maze task. The apparent densities of both N-methyl-D-aspartate/[125I]dizocilpine maleate and kainate binding sites were significantly decreased in various regions of the aged rat brain. Marked losses in [125I]dizocilpine maleate binding sites were observed in outer laminae of the frontal, parietal and temporal cortices, and the stratum radiatum of the CA3 subfield of the hippocampus. Interestingly, losses in [125I]dizocilpine maleate binding sites were generally most evident in the cognitively unimpaired aged subgroup, suggesting a possible inverse relationship between losses of this receptor subtype and cognitive performances in the Morris water maze task. The levels of [3H]kainate binding were most significantly diminished in various cortical and hippocampal areas as well as the striatum and septal nuclei of both groups of aged rats. In contrast, the apparent density of [3H]AMPA binding was increased in most hippocampal subfields and the superficial laminae of the occipital cortex of the cognitively impaired vs young adult rats. Changes in [3H]AMPA labeling failed to reach significance in the unimpaired cohort. Taken together, these results show that while losses in [3H]kainate binding were similar in both subgroups of aged rats, differences were seen with respect to cognitive status for both [125I]dizocilpine maleate/N-methyl-D-aspartate and [3H]AMPA binding sites. Decreases in [125I]dizocilpine maleate binding sites were mostly restricted to cortical areas of cognitively unimpaired rats, while increases in the AMPA binding subtype were seen in the memory-impaired subgroup. It would thus appear that changes in N-methyl-D-aspartate and AMPA receptor subtypes may be more critical than alterations in kainate binding sites for the emergence of the functional deficits seen in the aged cognitively impaired rat.

Aging↗

PubMed1995

Cholinergic markers in aged cognitively impaired Long-Evans rats.

Aged Long-Evans rats (24-25 months old) were classified into cognitively impaired or unimpaired subgroups based on their performances in the Morris Swim Maze task compared to young controls. Using quantitative in vitro receptor autoradiography, we investigated the status of various cholinergic markers in these two groups and in young adults (six months) animals. The apparent density of [3H]pirenzepine (muscarinic M1) sites was similar in the three groups of rats in various cortical areas, subfields of the hippocampus, medial septum and striatum. Similarly, choline acetyltransferase activity and the density of [3H]hemicholinium-3 (high-affinity choline uptake) and [3H]cytisine (nicotinic) binding sites were also unchanged in the brain regions studied between the aged cognitively impaired, unimpaired and young adult rats. In contrast, significant increases in [3H]AF-DX 384 (muscarinic M2) binding density were observed in various cortical areas and in the molecular layer of the dentate gyrus of aged cognitively impaired versus unimpaired rats and in few cortical regions of old as compared to young animals. Therefore, a selective alteration in the regulation of putative M2 receptor sites is apparent, particularly in the aged cognitively impaired rats. Increases in M2 binding sites could lead to a decrease in the capacity to release acetylcholine, as some of the M2 receptors are believed to act as negative autoreceptors. This could influence cognitive functions as selective M2 blockers have recently been reported to facilitate spatial memory in aged impaired rats [Doods et al. (1993) Life Sci. 52, 497-503: Quirion et al. (1995) J. Neurosci. 15, 1455-1462.

Aging↗

PubMed1995

Dopamine D1 receptor ligands modulate cognitive performance and hippocampal acetylcholine release in memory-impaired aged rats.

The possible modulation by D1 drugs of learning abilities of a population of aged memory-impaired animals was investigated in the present study. The level of D1/[3H]SCH 23390 receptors was first examined by quantitative autoradiography to ascertain if cognitive deficits seen in these animals could be related to alterations in the levels of these receptors. No significant differences in [3H]SCH 23390 binding were observed in any of the brain areas examined between young, and aged memory-unimpaired and aged memory-impaired animals. However, the cognitive deficits of the aged-impaired rats were modulated by D1 drugs. The D1 agonists SKF 38393 and SKF 81297 (3.0 mg/kg, i.p.) significantly reduced the latency period to find a hidden platform in the Morris Water Maze, reflecting improved cognitive functions, while the D1 antagonist SCH 23390 (0.05 mg/kg, i.p.) had no overall significant effect. Moreover, the D1 agonist SKF 38393 increased, whereas the antagonist inhibited, in vivo hippocampal acetylcholine release. Taken together, these results suggest that functional hippocampal acetylcholine-dopamine interactions exist in aged memory-impaired rats. More importantly, the cognitive deficits seen in the aged-impaired rats can be attenuated by stimulations of D1 receptors, hence suggesting an alternative approach to alleviate the cognitive deficits seen in the aged brain.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

Stimulation of CRH-mediated ACTH secretion by central administration of neurotensin: evidence for the participation of the paraventricular nucleus.

Central administration of neurotensin (NT) stimulates hypothalamic-pituitary-adrenal (HPA) activity in freely-moving rats. Increases in adrenocorticotropin hormone (ACTH) and corticosterone (B) were observed 15 min following central NT administration and remained elevated for up to 4 h. Of the two NT fragments tested, NT1-8 and NT8-13, only NT8-13 was found to significantly elevate ACTH and B levels. Moreover, NT8-13 activated the HPA axis with a temporal profile similar to NT1-13, suggesting an interaction with the pharmacologically and molecularly characterized NT receptor. Animals pre-treated intravenously with the corticotropin-releasing hormone (CRH) antagonist, alpha-helical CRH, showed attenuated plasma ACTH and B responses to central NT administration. This indicates that CRH receptor activation is necessary for the stimulatory effects of NT on HPA function. Bilateral lesions of the paraventricular nucleus (PVN) of the hypothalamus significantly reduced NT-induced stimulation of ACTH and B release suggesting that the PVN is essential for NT's stimulatory action. Median eminence content studies indicated that acute central NT administration stimulates CRH, but not arginine vassopressin (AVP), release in animals examined 60 min following NT injection. Taken together, these findings suggest that the stimulatory effects of NT on HPA activity occur via specific NT receptors and that one site of action of NT is likely at the level of the PVN where NT elicits the release of CRH.

Adrenocorticotropic Hormone↗

PubMed1995

Facilitation of acetylcholine release and cognitive performance by an M(2)-muscarinic receptor antagonist in aged memory-impaired.

Aged memory-impaired (AI) and unimpaired (AU) 24-25-month-old Long-Evans rats were used to investigate the integrity of various cholinergic markers during normal aging and to establish if alterations can possibly relate to cognitive disabilities. AI and AU rats were classified on the basis of their performance in the Morris swim maze task. Choline acetyltransferase activity (ChAT) was not differentially altered in various cortical and hippocampal areas between these two groups. Similarly, quantitative receptor autoradiography did not reveal significant differences in 3H-pirenzepine/muscarinic M1 and 3H-hemicholinium-3/high-affinity choline uptake binding sites in AI versus AU rats. In contrast, 3H-AF-DX 384/putative muscarinic M2 binding was significantly increased in certain cortical and hippocampal areas of the age-impaired animals. These increments were correlated with decreased in vivo acetylcholine (ACh) release capacity in the AI rats. Most interestingly, the muscarinic M2 antagonist BIBN-99 reversed, in a dose-dependent manner, the impaired ACh release as well as the cognitive deficits observed in the AI group. Similarly, BIBN-99 reversed scopolamine-induced amnesia in young animals. The efficacy of BIBN-99 likely relates to its antagonistic properties on negative muscarinic M2 autoreceptors that are apparently increased in the AI animals, leading to altered ACh release. Taken together, these findings strengthen the role of ACh in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic functions, such as Alzheimer's disease.

Acetylcholine↗

PubMed1995

Increased production of inositol phosphates and diacylglycerol in aged cognitively impaired rats after stimulation of muscarinic, metabotropic-glutamate and endothelin receptors.

Investigations of the functional integrity of receptor-mediated signal transduction are crucial to the understanding of the biochemical cascade underlying memory deficits and neurodegenerative processes of normal and pathological aging. In order to evaluate possible alterations in intracellular transduction components in aging, we studied two groups of 24- to 25-month-old Long-Evans rats selected on the basis of their cognitive performance in the Morris maze task, the aged, cognitively impaired (AI) and cognitively unimpaired (AU) animals. Production of diacylglycerol and inositol phosphates (IPs), two intracellular metabolites generated by the hydrolysis of phosphatidylinositol, were measured in selected brain areas after stimulation by various receptor agonists (1 mM carbachol, muscarinic receptors; 100 microM trans-1-aminocyclopentane-1, 3-dicarboxylate, metabotropic-glutamatergic receptors and 100 nM endothelin-1). Diacylglycerol and IPs were measured following the respective incorporation of [3H]cytidine and [3H]inositol. Data suggest that the stimulation of the inositide cascade via these receptors is at least preserved, or potentiated in the hippocampus and cortex of AI animals. Significant increases in [3H]cytidine and [3H]inositol incorporations were seen in these regions in AI vs. AU and young animals. It remains to be established if these modifications are related directly to the cognitive abilities of the aged rat as AU rats were often comparable to young animals in regard to inositide production. However, higher levels of incorporation in the AI group could reflect modifications in membrane fluidity and possibly increases in IP turnover. Because the IP cascade regulates intracellular Ca++ homeostasis, alterations of this pathway could have complex effects on normal cellular integrity as Ca++ equilibrium must be maintained for adequate neuronal viability and functions.

Aging↗

PubMed1995

Steroid effects on brain functions: an example of the action of glucocorticoids on central dopaminergic and neurotensinergic systems.

It is now clearly established that steroid hormones released from peripheral endocrine glands may, through specific receptors in the brain, directly regulate brain function. These effects may be rapid or involve long-term modifications at the genomic level. Concerning the glucocorticoids, their receptors are found in most neuronal cells, an observation which can be related to their widespread effects on neuronal metabolism. Furthermore, glucocorticoids are often related to stress. We have previously demonstrated that neonatal handling of the rat prevented excessive endocrine response to stress. In adults, this action appeared to protect the animal from potential damaging effects of glucocorticoids and from related impairment of cognitive functions. The effects of glucocorticoids are thought to involve an interaction of several central neurotransmitter systems. One such neurotransmitter is neurotensin, a neuropeptide which was reported to be closely related to central dopaminergic system regulation. This paper presents a rapid overview of the central effects of glucocorticoids and possible evidence for the interrelationship between these steroids, dopamine and neurotensin systems in the regulation of the hypothalamo-pituitary-adrenal axis. It provides a new way to approach stress responses and to develop new substances that may become potential drugs in the treatment of some psychiatric disorders.

Adrenocorticotropic Hormone↗

PubMed1994

Blockade of neurotensin binding in the rat hypothalamus and of the central action of neurotensin on the hypothalamic-pituitary-adrenal axis with non-peptide receptor antagonists.

Central administration of neurotensin (NT) has been shown to activate the hypothalamic-pituitary-adrenal axis, an effect which seems dependent upon the release of corticotropin-releasing factor. In this study, we describe the distribution of NT binding sites in the hypothalamus using film and emulsion receptor autoradiography. Among the 125I-NT-labelled hypothalamic nuclei, relatively high densities of neurotensin binding sites were detected over the paraventricular nucleus. Silver grains on emulsion-coated slides overlaid indiscriminately cell bodies and surrounding processes of magnocellular and parvocellular parts of the nucleus. Two newly developed NT receptor antagonists, SR 48692 and its analog SR 48450, competed for 125I-NT binding to hypothalamic tissue sections and membrane preparations with Ki values in the nanomolar range. Moreover, intracerebrally injected SR 48450 was able to block the NT-induced hypothalamic-pituitary-adrenal axis activation in freely moving rats, whereas its administration alone did not significantly affect basal plasma levels of adrenocorticotropin and corticosterone. These data provide anatomical substrate for a potential neurotensin action at the hypothalamus in the hypothalamic-pituitary-adrenal axis activation and highlight the use of new non-peptide NT receptor antagonists to characterize the effects of NT on neuroendrocrine functions.

Adrenocorticotropic Hormone↗

PubMed1994

Hypothalamic-pituitary-adrenal activity during chronic central administration of interleukin-2.

The cytokine interleukin-2 (IL-2) exerts numerous effects within the immune as well as the central nervous system and is thought to serve as a humoral signal in their communication. Brain-derived or blood-borne IL-2 may also control the activity of the hypothalamic-pituitary-adrenal (HPA) axis at various levels of regulation. In this study we investigated whether persistently elevated levels of central IL-2, which are associated with several diseases or induced during immunotherapeutic use of this cytokine, could induce long term activation of the HPA axis. Adult male Sprague-Dawley rats received an intracerebroventricular infusion of the recombinant cytokine at a rate of 5 U/h (equivalent to 2.5 ng/h or 162 fmol/h) by means of osmotic minipumps. Control animals received heat-inactivated IL-2. After 7 days of continuous infusion, blood samples were taken at intervals of 4 h over a period of 24 h, and plasma levels of ACTH and corticosterone (CORT) were determined. IL-2 caused a significant increase in ACTH levels during the later portion of the dark phase of the cycle. Plasma CORT concentrations were significantly elevated over almost the whole diurnal cycle. Measurements of CORT-binding globulin concentrations revealed IL-2-induced decreases during the dark phase, resulting in a marked increase in free CORT. Additionally, after 11 days of chronic infusion, both groups of animals underwent a 20-min restraint stress. IL-2-treated animals showed stress-induced increases in plasma ACTH and CORT that were not significantly different from those of animals treated with heat-inactivated IL-2. Along with the alteration of HPA activity seen in the IL-2-treated animals, chronic delivery of the cytokine caused periventricular tissue damage and gliosis. Taken together, the data reflect the capacity of IL-2 to modulate neuroendocrine activity over an extended period of treatment. Moreover, the IL-2-induced effects on HPA activity seen here may help to explain some of the endocrine disturbances seen in patients undergoing IL-2 immunotherapy.

Adrenocorticotropic Hormone↗