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Peripheral Administration (peripheral + administration)
Selected AbstractsCytokines and Cognition,The Case for A Head-to-Toe Inflammatory ParadigmJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2002Craig J. Wilson MBBS The brain is not only immunologically active of its own accord, but also has complex peripheral immune interactions. Given the central role of cytokines in neuroimmmunoendocrine processes, it is hypothesized that these molecules influence cognition via diverse mechanisms. Peripheral cytokines penetrate the blood-brain barrier directly via active transport mechanisms or indirectly via vagal nerve stimulation. Peripheral administration of certain cytokines as biological response modifiers produces adverse cognitive effects in animals and humans. There is abundant evidence that inflammatory mechanisms within the central nervous system (CNS) contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Cytokines mediate cellular mechanisms subserving cognition (e.g., cholinergic and dopaminergic pathways) and can modulate neuronal and glial cell function to facilitate neuronal regeneration or neurodegeneration. As such, there is a growing appreciation of the role of cytokine-mediated inflammatory processes in neurodegenerative diseases such as Alzheimer's disease and vascular dementia. Consistent with their involvement as mediators of bidirectional communication between the CNS and the peripheral immune system, cytokines play a key role in the hypothalamic-pituitary-adrenal axis activation seen in stress and depression. In addition, complex cognitive systems such as those that underlie religious beliefs, can modulate the effects of stress on the immune system. Indirect means by which peripheral or central cytokine dysregulation could affect cognition include impaired sleep regulation, micronutrient deficiency induced by appetite suppression, and an array of endocrine interactions. Given the multiple levels at which cytokines are capable of influencing cognition it is plausible that peripheral cytokine dysregulation with advancing age interacts with cognitive aging. [source] Cholecystokinin receptor antagonists increase the rat pup's preference toward maternal-odor and rug textureDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2001Michal Shayit Abstract The role of the cholecystokinin (CCK) system in mediating the infant's natural preferences toward maternal-related stimuli was examined by peripheral administration of selective CCKA and CCKB receptor antagonists (Devazepide and L-365,260, respectively) to 11,12-day-old rats and presenting them with a 3-minute preference test. In Experiment 1, the choice was between two floor textures, rug and plywood; the time spent on the relatively preferred side (rug) was measured. In Experiment 2, the odor of maternal faces emanated from one end of the test arena; time spent near that end was measured. These sensory stimuli were chosen as they represent olfactory and tactile aspects of the dam and nest. Compared to controls, both CCK receptor antagonists selectively increased the time spent on the preferred side, in both experiments, without affecting axillary temperature or locomotor activity. The results suggest that CCK may mediate and attenuate the infant's attraction toward naturally preferred stimuli. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 38: 164,173, 2001 [source] Possible mechanisms for the anticonvulsant activity of fructose-1,6-diphosphateEPILEPSIA, Issue 2008Janet L. Stringer Summary Fructose-1,6-diphosphate (FDP), an intracellular metabolite of glucose, has anticonvulsant activity in several models of acute seizures in laboratory animals. The anticonvulsant effect of FDP is most likely due to a direct effect since intraperitoneal and oral administration results in significant increases in brain levels. A number of mechanisms have been proposed for this action of FDP. One possibility is that peripheral administration of FDP results in changes in brain metabolism that are anticonvulsant. Glucose can be metabolized through the glycolytic or pentose phosphate pathway. There is evidence that the pentose phosphate pathway is more active in the brain than in other tissues, and that, in the presence of elevated levels of FDP, the majority of glucose is metabolized by the pentose phosphate pathway. The pentose phosphate pathway generates NADPH, which is used to reduce glutathione. The reduced form of endogenous glutathione has been shown to have anticonvulsant activity. Taken together, the data suggest a hypothesis that exogenously administered FDP gets into the brain and astrocytes where it increases the flux of glucose through the pentose phosphate pathway, generating additional NADPH for the reduction of glutathione. [source] Thyrotrophin-Releasing Hormone Decreases Feeding and Increases Body Temperature, Activity and Oxygen Consumption in Siberian HamstersJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2007S. Schuhler Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5,50 mg/kg body weight; i.p.) and central (0.5 µg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function. [source] ,1 Adrenoreceptors Mediate The Stimulatory Effects of Oestrogen On Stress-Related Hypothalamic-Pituitary-Adrenal Activity in The Female RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2004V. Viau Abstract Variation in challenge-induced adrenocorticotropin hormone (ACTH) release over the oestrous cycle occurs in response to fluctuations in circulating concentrations of oestrogen and progesterone. However, how these ovarian steroids interact to regulate the principal ACTH cosecretagogues, corticotropin-releasing hormone (CRH) and arginine vasopressin is not understood. Here, we measured median eminence CRH and vasopressin content in intact cycling female rats, and in ovariectomized (OVX) females steroid-replaced in a manner that approximates the relative release patterns of oestrogen and progesterone seen over the oestrous cycle. Intact cycling females showed significantly higher median eminence CRH and vasopressin concentrations during proestrous and oestrous compared to the diestrous phase. In OVX rats, a single 10 µg injection of oestrogen failed to mimic this increase in median eminence CRH and vasopressin. However, this dose significantly elevated CRH and vasopressin content in OVX rats previously exposed to diestrous concentrations of oestrogen and progesterone. Moreover, oestrogen priming enhanced restraint-induced depletion of CRH and vasopressin from the median eminence, but only against a background of low oestrogen and progesterone replacement. Oestrogen-induced elevations in median eminence vasopressin (but not CRH) content were reduced by peripheral administration of the ,1 adrenoreceptor antagonist prazosin. Finally, plasma ACTH concentrations following central injection of the ,1 receptor agonist, phenylephrine, were significantly higher in rats during proestrous compared to diestrous. These results indicate that the stimulatory effect of oestrogen on both the expression and stress-induced release of ACTH cosecretagogues is exerted only against a background of low oestrogen and progesterone levels, and is mediated, in part, via the ,1 adrenoreceptor. [source] Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociceptionBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2010S Bang BACKGROUND AND PURPOSE Temperature-sensitive transient receptor potential ion channels (thermoTRPs) expressed in primary sensory neurons and skin keratinocytes play a crucial role as peripheral pain detectors. Many natural and synthetic ligands have been found to act on thermoTRPs, but little is known about endogenous compounds that inhibit these TRPs. Here, we asked whether resolvin D1 (RvD1), a naturally occurring anti-inflammatory and pro-resolving lipid molecule is able to affect the TRP channel activation. EXPERIMENTAL APPROACH We examined the effect of RvD1 on the six thermoTRPs using Ca2+ imaging and whole cell electrophysiology experiments using the HEK cell heterologous expression system, cultured sensory neurons and HaCaT keratinocytes. We also checked changes in agonist-specific acute licking/flicking or flinching behaviours and TRP-related mechanical and thermal pain behaviours using Hargreaves, Randall-Selitto and von Frey assay systems with or without inflammation. KEY RESULTS RvD1 inhibited the activities of TRPA1, TRPV3 and TRPV4 at nanomolar and micromolar levels. Consistent attenuations in agonist-specific acute pain behaviours by immediate peripheral administration with RvD1 were also observed. Furthermore, local pretreatment with RvD1 significantly reversed mechanical and thermal hypersensitivity in inflamed tissues. CONCLUSIONS AND IMPLICATIONS RvD1 was a novel endogenous inhibitor for several sensory TRPs. The results of our behavioural studies suggest that RvD1 has an analgesic potential via these TRP-related mechanisms. [source] | ||||||||||