Thermoregulation in the rabbit following intracranial injection of norepinephrine

1975 ◽  
Vol 229 (3) ◽  
pp. 676-682 ◽  
Author(s):  
E Preston

The release of norepinephrine (NE) from nerve terminals in the anterior hypothalamic/preoptic area (AH/POA) of the rabbit may serve to raise body temperature. To further examine the putative neurotransmitter role of NE, bilateral microinjections of 5 or 10 mug NE were made into or near the AH/POA of 44 conscious rabbits exposed to an ambient temperature of 15 degrees C. Microinjections into the AH/POS did not cause fever; they either had no influence on thermoregulation or rapidly induced ear vasocilation and increased ear temperature accompanied by slight falls in rectal temperature. The latter averaged 0.32 degrees C (range: 0.16-0.45 degrees C) in 18 rabbits in which the effects were prominent. In contrast, the injection of 100 or 250 mug NE into the lateral cerebral ventricles of conscious rabbits in the 15 degrees C environment caused mean fevers of 0.62 +/- 0.0, and 1.04 +/- 0.14 degrees C (+/- SE, n equals 6), respectively, within 70 min. The febrile response to intraventricular injection of NE may be due to an action of the drug at a site other than the AH/POA. Alternatively, the response may depend critically on the particular distribution of NE that results from its diffusion from the third ventricle into the AH/POA.

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 323-335 ◽  
Author(s):  
Bruna Kalil ◽  
Aline B. Ribeiro ◽  
Cristiane M. Leite ◽  
Ernane T. Uchôa ◽  
Ruither O. Carolino ◽  
...  

Abstract In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.


2021 ◽  
Vol 15 ◽  
Author(s):  
Sarah L. Reitz ◽  
Max B. Kelz

The role of the hypothalamic preoptic area (POA) in arousal state regulation has been studied since Constantin von Economo first recognized its importance in the early twentieth century. Over the intervening decades, the POA has been shown to modulate arousal in both natural (sleep and wake) as well as drug-induced (anesthetic-induced unconsciousness) states. While the POA is well known for its role in sleep promotion, populations of wake-promoting neurons within the region have also been identified. However, the complexity and molecular heterogeneity of the POA has made distinguishing these two populations difficult. Though multiple lines of evidence demonstrate that general anesthetics modulate the activity of the POA, the region’s heterogeneity has also made it challenging to determine whether the same neurons involved in sleep/wake regulation also modulate arousal in response to general anesthetics. While a number of studies show that sleep-promoting POA neurons are activated by various anesthetics, recent work suggests this is not universal to all arousal-regulating POA neurons. Technical innovations are making it increasingly possible to classify and distinguish the molecular identities of neurons involved in sleep/wake regulation as well as anesthetic-induced unconsciousness. Here, we review the current understanding of the POA’s role in arousal state regulation of both natural and drug-induced forms of unconsciousness, including its molecular organization and connectivity to other known sleep and wake promoting regions. Further insights into the molecular identities and connectivity of arousal-regulating POA neurons will be critical in fully understanding how this complex region regulates arousal states.


2000 ◽  
Vol 278 (5) ◽  
pp. R1275-R1281 ◽  
Author(s):  
Irene R. Pelá ◽  
Márcia E. S. Ferreira ◽  
Miriam C. C. Melo ◽  
Carlos A. A. Silva ◽  
Márcio M. Coelho ◽  
...  

Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory actions in the mammalian central nervous system (CNS). Like the cytokines, PDGF primarily signals through tyrosine phosphorylation-dependent pathways that activate multiple intracellular molecules including Janus family kinases. We previously showed that microinjection of PDGF-BB into the lateral ventricle induced a febrile response in rats that was reduced by pretreatment with Win 41662, a potent inhibitor of PDGF receptors (Pelá IR, Ferreira MES, Melo MCC, Silva CAA, and Valenzuela CF. Ann NY Acad Sci 856: 289–293, 1998). In this study, we further characterized the role of PDGF-BB in the febrile response in rats. Microinjection of PDGF-BB into the third ventricle produced a dose-dependent increase in colonic temperature that peaked 3–4 h postinjection. Win 41662 attenuated fever induced by intraperitoneal injection of bacterial lipopolysaccharide, suggesting that endogenous PDGF participates in the febrile response to this exogenous pyrogen. Importantly, febrile responses induced by tumor necrosis factor-α, interleukin-1β, and interleukin-6 were unchanged by Win 41662. Both indomethacin and dexamethasone blocked the PDGF-BB-induced increase in colonic temperature, and, therefore, we postulate that PDGF-BB may act via prostaglandin- and/or inducible enzyme-dependent pathways. Thus our findings suggest that PDGF-BB is an endogenous CNS mediator of the febrile response in rats.


1986 ◽  
Vol 251 (5) ◽  
pp. R823-R832
Author(s):  
D. Mok ◽  
G. J. Mogenson

Spontaneous extracellular activity was recorded from single neurons in the rostral zona incerta (ZI) of urethan-anesthetized rats. Ventricular injections of hyperosmotic saline (1 or 2 microliter of NaCl solutions with osmolarities of 0.6 or 1.2 osmol/l) and distilled water (1 or 2 microliter) at the level of the anteroventral third ventricle (AV3V) changed the firing rate of ZI neurons. By comparison, ventricular injections of osmotic solutions at the level of the dorsal third ventricle were relatively ineffective. Injections of osmotic solutions (0.2 or 0.5 microliter of 1.2 osmol/l NaCl) into the medial preoptic area (MPO) also changed the firing rate of ZI neurons, whereas control injections into the caudate putamen were ineffective. In another series of rats, injections of procaine into the region of the rostral ZI significantly reduced drinking to injections of hyperosmotic saline into the ipsi- but not the contralateral MPO. The ZI, AV3V, and MPO have previously been reported to contribute to the neural regulation of fluid intake. These findings provide additional evidence for a role of the ZI in drinking and suggest that part of the central pathway for osmotic thirst involves a projection to neurons in the ZI from osmoreceptors in the MPO.


1987 ◽  
Vol 65 (6) ◽  
pp. 1255-1260 ◽  
Author(s):  
C. M. Blatteis ◽  
J. R. S. Hales ◽  
M. J. McKinley ◽  
A. A. Fawcett

Ablation of the anteroventral third ventricle (AV3V) region, which includes the organum vasculosum laminae terminalis (OVLT), blocks the febrile response of guinea pigs to systemically injected endotoxin; by contrast, discrete lesions of the OVLT transiently enhance fever in rabbits and rats. To assess whether separate subdivisions of the AV3V may mediate these different effects, the thermal responses to Escherichia coli lipopolysaccharide (LPS, 0.25 μg/kg, i.v.) were measured in eight sheep before and 12–13 days after placement of lesions at various levels within the AV3V. The responses of four of these sheep to crude homologous endogenous pyrogen (EP, 1–2 mL, i.c.v.) were also evaluated. Additionally, five other sheep were tested with LPS 2–8 months postlesion. All the experiments were performed at thermoneutrality. Sheep were used because most of the frontal wall of their 3V forms an elongated OVLT consisting of an avascular body and a vascular base. The animals were classified postmortem according to the extent of tissue ablated. Lesion overlap analyses showed that (i) medial lesions which extended from the floor of the 3V to the anterior commissure and laterally into adjacent preoptic periventricular tissue were associated with significantly depressed fever after LPS (n = 2); (ii) comparable lesions, but which excluded the ventral portion of the AV3V, i.e., the base of the OVLT, did not alter the magnitude of the febrile response to LPS (n = 4); (iii) lesions of the lateral walls of the 3V and (or) of the adjacent medial preoptic and anterior hypothalamic areas but excluding the frontal 3V wall also did not affect fever height after LPS (n = 7). Damage to aspects of the walls of the lateral ventricles attenuated the febrile response to EP i.c.v. (n = 3). Hence, although no separate fever-inhibiting and fever-enhancing regions were found within the AV3V, these results indicate that the ventral portion of the AV3V, i.e., the vascular plexus of the OVLT, is critical for normal fever development in sheep.


Author(s):  
Alison Carrol

In 1918 the end of the First World War triggered the return of Alsace to France after almost fifty years of annexation into the German Empire. Enthusiastic crowds in Paris and Alsace celebrated the homecoming of the so-called lost province, but return proved far less straightforward than anticipated. The region’s German-speaking population demonstrated strong commitment to local cultures and institutions, as well as their own visions of return to France. As a result, the following two decades saw politicians, administrators, industrialists, cultural elites, and others grapple with the question of how to make Alsace French again. The answer did not prove straightforward; differences of opinion emerged both inside and outside the region, and reintegration became a fiercely contested process that remained incomplete when war broke out in 1939. The Return of Alsace to France examines this story. Drawing upon national, regional, and local archives, it follows the difficult process of Alsace’s reintegration into French society, culture, political and economic systems, and legislative and administrative institutions. It connects the microhistory of the region with the macro levels of national policy, international relations, and transnational networks, and with the cross-border flows of ideas, goods, people, and cultural products that shaped daily life in Alsace. Revealing Alsace to be a site of exchange between a range of interest groups with different visions of the region’s future, this book underlines the role of regional populations and cross-border interactions in forging the French Third Republic.


2020 ◽  
Vol 402 (1) ◽  
pp. 89-98
Author(s):  
Nathalie Meiser ◽  
Nicole Mench ◽  
Martin Hengesbach

AbstractN6-methyladenosine (m6A) is the most abundant modification in mRNA. The core of the human N6-methyltransferase complex (MTC) is formed by a heterodimer consisting of METTL3 and METTL14, which specifically catalyzes m6A formation within an RRACH sequence context. Using recombinant proteins in a site-specific methylation assay that allows determination of quantitative methylation yields, our results show that this complex methylates its target RNAs not only sequence but also secondary structure dependent. Furthermore, we demonstrate the role of specific protein domains on both RNA binding and substrate turnover, focusing on postulated RNA binding elements. Our results show that one zinc finger motif within the complex is sufficient to bind RNA, however, both zinc fingers are required for methylation activity. We show that the N-terminal domain of METTL3 alters the secondary structure dependence of methylation yields. Our results demonstrate that a cooperative effect of all RNA-binding elements in the METTL3–METTL14 complex is required for efficient catalysis, and that binding of further proteins affecting the NTD of METTL3 may regulate substrate specificity.


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