Peptide neurohormones: their role in thermoregulation and fever

1983 ◽  
Vol 61 (7) ◽  
pp. 579-593 ◽  
Author(s):  
W. D. Ruwe ◽  
W. L. Veale ◽  
K. E. Cooper
Keyword(s):  
Body Temperature ◽  
Anterior Commissure ◽  
Extracellular Fluid ◽  
Current Evidence ◽  
Central Administration ◽  
Febrile Response ◽  
Axonal Projections ◽  
The Central Nervous System ◽  
Convulsive Disorders ◽  
The Brain

The neural elements of the rostral diencephalon in the mammal have been implicated in the regulation of body temperature. Moreover, it may be the neural elements within this region of the brain which activate the febrile mechanisms in response to pyrogen. Is it possible that the neuropeptides located within this area of the brain serve as neurochemical intermediaries involved in temperature regulation, fever, and (or) antipyresis? Central administration of several neuropeptides can elicit marked changes in the core temperature of an animal. Although most of these purative neuroregulators exert only a very minor influence on thermoregulation, a small number of the neuropeptides have been shown to have a profound effect on the system controlling this basic vegetative function. One of these peptides, arginine vasopressin (AVP) may play a role as an endogenous antipyretic. The neuroanatomical localization of this peptide, as well as its axonal projections, are consistent with such a role for this neurohypophyseal peptide in the mediation of antipyresis. In addition, current evidence suggests that AVP does function as a neurotransmitter. Examination of the febrile response to pyrogen in both the periparturient animal and the neonate indicates that an elevation in plasma levels of AVP is closely correlated with the diminution in the febrile response. Also, when AVP is perfused into punctate regions of the brain, a pyrogen-induced fever may be markedly suppressed. AVP appears to act primarily within the septal area, 2- to 3-mm rostral to the anterior commissure. During the development of fever, the release of AVP is altered within these same loci. As body temperature decreases during the febrile state, there is a concomitant increase in the amount of AVP released into the extracellular fluid of these septal sites. Very recent findings suggest that AVP may have additional central neurochemical functions. For example, this peptide may be involved in the etiology of some forms of convulsive disorders. The precise manner in which body temperature is regulated by the central nervous system normally and during fever is not well understood. In particular, the central mechanism of action of AVP in these processes remains to be determined. Currently, it is clear that the critical central mechanisms which are active in thermoregulation and fever are quite complex and will require many more years of investigation before the exact role of each can be enunciated.

scholarly journals Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction

2017 ◽  
Vol 114 (36) ◽  
pp. 9731-9736 ◽  
Author(s):  
Rigo Cintron-Colon ◽  
Manuel Sanchez-Alavez ◽  
William Nguyen ◽  
Simone Mori ◽  
Ruben Gonzalez-Rivera ◽  
...  
Keyword(s):  
Growth Factor ◽  
Body Temperature ◽  
Calorie Restriction ◽  
Core Body Temperature ◽  
Insulin Like Growth Factor ◽  
Hypothalamic Nuclei ◽  
The Central Nervous System ◽  
Temperature Homeostasis ◽  
Core Body ◽  
The Brain

When food resources are scarce, endothermic animals can lower core body temperature (Tb). This phenomenon is believed to be part of an adaptive mechanism that may have evolved to conserve energy until more food becomes available. Here, we found in the mouse that the insulin-like growth factor 1 receptor (IGF-1R) controls this response in the central nervous system. Pharmacological or genetic inhibition of IGF-1R enhanced the reduction of temperature and of energy expenditure during calorie restriction. Full blockade of IGF-1R affected female and male mice similarly. In contrast, genetic IGF-1R dosage was effective only in females, where it also induced transient and estrus-specific hypothermia in animals fed ad libitum. These effects were regulated in the brain, as only central, not peripheral, pharmacological activation of IGF-1R prevented hypothermia during calorie restriction. Targeted IGF-1R knockout selectively in forebrain neurons revealed that IGF signaling also modulates calorie restriction-dependent Tbregulation in regions rostral of the canonical hypothalamic nuclei involved in controlling body temperature. In aggregate, these data identify central IGF-1R as a mediator of the integration of nutrient and temperature homeostasis. They also show that calorie restriction, IGF-1R signaling, and body temperature, three of the main regulators of metabolism, aging, and longevity, are components of the same pathway.

Site-specific modulation of LPS-induced fever and interleukin-1β expression in rats by interleukin-10

2002 ◽  
Vol 282 (6) ◽  
pp. R1762-R1772 ◽  
Author(s):  
Annemarie Ledeboer ◽  
Rob Binnekade ◽  
John J. P. Brevé ◽  
John G. J. M. Bol ◽  
Fred J. H. Tilders ◽  
...  
Keyword(s):  
Brain Stem ◽  
Interleukin 10 ◽  
Primary Site ◽  
Central Administration ◽  
Febrile Response ◽  
Peripheral Tissues ◽  
Site Specific ◽  
Intracerebroventricular Infusion ◽  
The Brain ◽  
Anti Inflammatory Cytokine

Bacterial lipopolysaccharide (LPS) induces fever that is mediated by pyrogenic cytokines such as interleukin (IL)-1β. We hypothesized that the anti-inflammatory cytokine IL-10 modulates the febrile response to LPS by suppressing the production of pyrogenic cytokines. In rats, intravenous but not intracerebroventricular infusion of IL-10 was found to attenuate fever induced by peripheral administration of LPS (10 μg/kg iv). IL-10 also suppressed LPS-induced IL-1β production in peripheral tissues and in the brain stem. In contrast, central administration of IL-10 attenuated the febrile response to central LPS (60 ng/rat icv) and decreased IL-1β production in the hypothalamus and brain stem but not in peripheral tissues and plasma. Furthermore, intravenous LPS upregulated expression of IL-10 receptor (IL-10R1) mRNA in the liver, whereas intracerebroventricular LPS enhanced IL-10R1 mRNA in the hypothalamus. We conclude that IL-10 modulates the febrile response by acting in the periphery or in the brain dependent on the primary site of inflammation and that its mechanism of action most likely involves inhibition of local IL-1β production.

Involvement of brain cytokines in zymosan-induced febrile response

2014 ◽  
Vol 116 (9) ◽  
pp. 1220-1229 ◽  
Author(s):  
Amanda L. Bastos-Pereira ◽  
Daniel Fraga ◽  
Daniela Ott ◽  
Björn Simm ◽  
Jolanta Murgott ◽  
...  
Keyword(s):  
Time Course ◽  
Calcium Concentration ◽  
Febrile Response ◽  
Tnf Α ◽  
Heat Conservation ◽  
The Central Nervous System ◽  
Factor Α ◽  
The Brain ◽  
Circulating Levels ◽  
Necrosis Factor

This study compared the involvement of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) within the central nervous system (CNS) in the febrile response induced by zymosan (zym) and lipopolysaccharide (LPS). In addition, we investigated whether zym could activate important regions related to fever; namely, the vascular organ of the laminae terminalis (OVLT) and the median preoptic nucleus (MnPO). Intraperitoneal injection of zym (1, 3, and 10 mg/kg) induced a dose-related increase in core temperature. Zym (3 mg/kg) also reduced tail skin temperature, suggesting the activation of heat conservation mechanisms, as expected, during fever. LPS increased plasma levels of TNF-α measured at 1 h, IL-1β measured at 2 h, and IL-6 measured at 3 h after injection. Zym increased circulating levels of IL-6 but not those of TNF-α or IL-1β at the same time points. In addition, an intracerebroventricular injection of antibodies against TNF-α (2.5 μg) and IL-6 (10 μg) or the IL-1 receptor antagonist (160 ng) reduced the febrile response induced by zym and LPS. Zym (100 μg/ml) also increased intracellular calcium concentration in the OVLT and MnPO from rat primary neuroglial cultures and increased release of TNF-α and IL-6 into the supernatants of these cultures. Together, these results suggest that TNF-α, IL-1β, and IL-6 within the CNS participate in the febrile response induced by zym. However, the time course of release of these cytokines may be different from that of LPS. In addition, zym can directly activate the brain areas related to fever.

scholarly journals Blood-Brain Barrier Overview: Structural and Functional Correlation

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Abeer Alahmari
Keyword(s):  
Blood Brain Barrier ◽  
Extracellular Fluid ◽  
Vital Role ◽  
Brain Barrier ◽  
Comprehensive Overview ◽  
Functional Correlation ◽  
Blood Brain ◽  
The Central Nervous System ◽  
And Function ◽  
The Brain

The blood-brain barrier (BBB) is a semipermeable and extremely selective system in the central nervous system of most vertebrates, that separates blood from the brain’s extracellular fluid. It plays a vital role in regulating the transport of necessary materials for brain function, furthermore, protecting it from foreign substances in the blood that could damage it. In this review, we searched in Google Scholar, Pubmed, Web of Science, and Saudi Digital Library for the various cells and components that support the development and function of this barrier, as well as the different pathways to transport the various molecules between blood and the brain. We also discussed the aspects that lead to BBB dysfunction and its neuropathological consequences, with the identification of some of the most important biomarkers that might be used as a biomarker to predict the BBB disturbances. This comprehensive overview of BBB will pave the way for future studies to focus on developing more specific targeting systems in material delivery as a future approach that assists in combinatorial therapy or nanotherapy to destroy or modify this barrier in pathological conditions such as brain tumors and brain stem cell carcinomas.

scholarly journals Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain.

1990 ◽  
Vol 172 (4) ◽  
pp. 1127-1132 ◽  
Author(s):  
S Perlman ◽  
G Evans ◽  
A Afifi
Keyword(s):  
Olfactory Bulb ◽  
Hepatitis Virus ◽  
Anterior Commissure ◽  
Olfactory Pathway ◽  
Surgical Ablation ◽  
Viral Transport ◽  
The Central Nervous System ◽  
Trigeminal Nerves ◽  
The Brain

Previous results suggested that, after intranasal inoculation, mouse hepatitis virus (MHV), a neurotropic coronavirus, entered the central nervous system (CNS) via the olfactory and trigeminal nerves. To prove this hypothesis, the effect of interruption of the olfactory pathway on spread of the virus was studied using in situ hybridization. Unilateral surgical ablation of this pathway prevented spread of the virus via the olfactory tract on the side of the lesion. MHV RNA could be detected, however, at distal sites on the operated side, indicating that the virus spread via well-described circuits involving the anterior commissure from the control (intact) side of the brain. Viral transport via the trigeminal nerve was not affected by removal of the olfactory bulb, showing that the surgical procedure was specific for the olfactory pathway. These results prove conclusively that MHV gains entry to the CNS via a transneuronal route, and spreads to additional sites in the brain via known neuroanatomic pathways.

scholarly journals IL-1 is a mediator of increases in slow-wave sleep induced by CRH receptor blockade

2000 ◽  
Vol 279 (3) ◽  
pp. R793-R802 ◽  
Author(s):  
Fang-Chia Chang ◽  
Mark R. Opp
Keyword(s):  
Hpa Axis ◽  
Slow Wave ◽  
Tumor Necrosis ◽  
Slow Wave Sleep ◽  
Central Administration ◽  
Regulatory Systems ◽  
The Central Nervous System ◽  
Factor Α ◽  
The Brain ◽  
Necrosis Factor

We hypothesize that corticotropin-releasing hormone (CRH), a regulator of the hypothalamic-pituitary-adrenal (HPA) axis, is involved in sleep-wake regulation on the basis of observations that the CRH receptor antagonist astressin, after a delay of several hours, reduces waking and increases slow-wave sleep (SWS) in rats. This delay suggests a cascade of events that begins with the HPA axis and culminates with actions on sleep regulatory systems in the central nervous system. One candidate mediator in the brain for these actions is interleukin (IL)-1. IL-1 promotes sleep, and glucocorticoids inhibit IL-1 synthesis. In this study, central administration of 12.5 μg astressin into rats before dark onset reduced corticosterone 4 h after injection and increased mRNA expression for IL-1α and IL-1β but not for IL-6 or tumor necrosis factor-α in the brain 6 h after injection. To determine directly whether IL-1 is involved in astressin-induced alterations in sleep-wake behavior, we then pretreated rats with 20 μg anti-IL-1β antibodies before injecting astressin. The increase in SWS and the reduction in waking that occur after astressin are abolished when animals are pretreated with anti-IL-1β. These data indicate that IL-1 is a mediator of astressin-induced alterations in sleep-wake behavior.

scholarly journals Perivascular and Perineural Pathways Involved in Brain Delivery and Distribution of Drugs after Intranasal Administration

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 598 ◽  
Author(s):  
Jeffrey J. Lochhead ◽  
Thomas P. Davis
Keyword(s):  
Current Evidence ◽  
Perivascular Spaces ◽  
Brain Delivery ◽  
Physiological Conditions ◽  
Routes Of Administration ◽  
Disease States ◽  
Efficient Delivery ◽  
The Central Nervous System ◽  
Trigeminal Nerves ◽  
The Brain

One of the most challenging aspects of treating disorders of the central nervous system (CNS) is the efficient delivery of drugs to their targets within the brain. Only a small fraction of drugs is able to cross the blood–brain barrier (BBB) under physiological conditions, and this observation has prompted investigation into the routes of administration that may potentially bypass the BBB and deliver drugs directly to the CNS. One such route is the intranasal (IN) route. Increasing evidence has suggested that intranasally-administered drugs are able to bypass the BBB and access the brain through anatomical pathways connecting the nasal cavity to the CNS. Though the exact mechanisms regulating the delivery of therapeutics following IN administration are not fully understood, current evidence suggests that the perineural and perivascular spaces of the olfactory and trigeminal nerves are involved in brain delivery and cerebral perivascular spaces are involved in widespread brain distribution. Here, we review evidence for these delivery and distribution pathways, and we address questions that should be resolved in order to optimize the IN route of administration as a viable strategy to treat CNS disease states.

Interaction between norepinephrine and prostaglandin E2 in the preoptic area of guinea pigs

1996 ◽  
Vol 271 (3) ◽  
pp. R528-R536 ◽  
Author(s):  
E. Sehic ◽  
A. L. Ungar ◽  
C. M. Blatteis
Keyword(s):  
Cerebrospinal Fluid ◽  
Body Temperature ◽  
Prostaglandin E2 ◽  
Intravenous Injection ◽  
Guinea Pigs ◽  
Preoptic Area ◽  
Extracellular Fluid ◽  
Low Ph ◽  
Febrile Response ◽  
Artificial Cerebrospinal Fluid

The release of norepinephrine (NE) and prostaglandin E2 (PGE2) in the preoptic-anterior hypothalamus (POA) by systemically administered pyrogens suggests that both substances may mediate the febrile response. To investigate their possible interaction, we measured directly the levels of PGE2 in the extracellular fluid of the POA of conscious guinea pigs microdialyzed intrapreoptically with exogenous NE over the entire course of their febrile response to endotoxin. Acidified and buffered NE (NEa, NEb), artificial cerebrospinal fluid (aCSFa, aCSFb), and vehicle (Veha, Vehb) were tested. All but aCSFb depressed the febrile response to endotoxin. The microdialysis of aCSFa, aCSFb, Veha, Vehb, and NEa did not change basal preoptic PGE2 levels. However, NEb, at a dose that by itself did not affect body temperature (Tb), caused a large elevation in preoptic PGE2. The intravenous injection of endotoxin increased the level of PGE2 in the POA. NEb potentiated this increase, whereas NEa, aCSFa, and Vehb reduced it; Veha reduced it for the first 60 min and enhanced it for the last 90 min of the experiment. Thus these data suggest that the low pH of the NE solute and/or its Veh may confound the observed effects of NE on the Tb and preoptic PGE2 induced by endotoxin. We surmise that this is due to a neurotoxic action of the antioxidants and the acidity of the solution on thermosensitive neurons in the POA. Hence, the results of experiments using exogenous, usually acidified, NE preparations that often also contain additives should be interpreted with caution.

scholarly journals Tight Junction Modulating Bioprobes for Drug Delivery System to the Brain: A Review

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1236
Author(s):  
Keisuke Tachibana ◽  
Yumi Iwashita ◽  
Erika Wakayama ◽  
Itsuki Nishino ◽  
Taiki Nishikaji ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Extracellular Fluid ◽  
Transport Systems ◽  
Brain Extracellular Fluid ◽  
The Central Nervous System ◽  
Polarized Transport ◽  
The Brain

The blood-brain barrier (BBB), which is composed of endothelial cells, pericytes, astrocytes, and neurons, separates the brain extracellular fluid from the circulating blood, and maintains the homeostasis of the central nervous system (CNS). The BBB endothelial cells have well-developed tight junctions (TJs) and express specific polarized transport systems to tightly control the paracellular movements of solutes, ions, and water. There are two types of TJs: bicellular TJs (bTJs), which is a structure at the contact of two cells, and tricellular TJs (tTJs), which is a structure at the contact of three cells. Claudin-5 and angulin-1 are important components of bTJs and tTJs in the brain, respectively. Here, we review TJ-modulating bioprobes that enable drug delivery to the brain across the BBB, focusing on claudin-5 and angulin-1.

Central arginine vasopressin and endogenous antipyresis

1992 ◽  
Vol 70 (5) ◽  
pp. 786-790 ◽  
Author(s):  
Quentin J. Pittman ◽  
Marshall F. Wilkinson
Keyword(s):  
Blood Pressure ◽  
Body Temperature ◽  
Arginine Vasopressin ◽  
Septal Area ◽  
Host Defence ◽  
Neonatal Rat ◽  
Prostaglandin E ◽  
Febrile Response ◽  
Arterial Blood ◽  
The Brain

Arginine vasopressin (AVP) is a centrally synthesized nonapeptide that exerts classical endocrine effects as well as a host of centrally mediated actions. A strong case can be argued in support of a neurotransmitter–neuromodulator role for AVP. Acting within the central nervous system (CNS), AVP has been demonstrated to be involved in the modulation of febrile body temperature. Because AVP acts to reduce pyrogen-induced fevers, but not normal body temperature, its actions are deemed to be antipyretic. However, to demonstrate an endogenous antipyretic function, AVP must be shown to be active during conditions where fever is naturally suppressed. This review will focus on five such conditions where the absence of pyrogen-induced fever can be linked to the endogenous activity of AVP within the brain. In the neonatal rat pup, the use of specific antagonists to the AVP receptor has revealed a role for CNS AVP in the absence of fever following peripheral injections of bacterial endotoxin. These results may help to explain a similar lack of fever in other newborn species. In parturient animals a reduced or absent febrile response has been linked to the increased presence of AVP within the septal area of the brain. The combined use of AVP receptor antagonism as well as immunohistochemistry has shown enhanced AVP activity within the ventral septal area of the rat and guinea pig brain during tolerance to intravenous pyrogens. These results suggest that the mechanism of fever suppression following repeated systemic injections of bacterial pyrogen includes centrally acting AVP. Recent observations from our laboratory have revealed a suppression of fever during the rising phase of arterial blood pressure in the one-kidney, one-clip model of hypertension. The normal febrile response to prostaglandin E1 can be restored in this instance by blockade of ventral septal AVP receptors. A similar situation of lack of response to pyrogens occurs in hypotensive animals in which pressor mechanisms are activated to restore blood pressure to normal. In this, and the previous four examples, centrally acting AVP has been linked to the natural suppression of pyrogen-induced fevers. Using these models of endogenous antipyresis we will continue to investigate this phenomenon to assess the benefits to the organism as well as to examine other nonthermal host defence responses.Key words: fever, antipyretic, pyrogen, host defence, vasopressin.

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