scholarly journals 0428 Taiep Rats Had Normal Levels of Orexin Neurons in the Lateral Hypothalamus But Their Cataplexy Attacks are Sensible to Specific Orexin B Agonist

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A164-A164
Author(s):  
J R Eguibar ◽  
C Cortes ◽  
K Espinoza ◽  
C I De Ovando
Keyword(s):  
Lateral Hypothalamus ◽  
Theta Rhythm ◽  
Muscle Tone ◽  
Central Administration ◽  
Sprague Dawley ◽  
Sudden Loss ◽  
Normal Number ◽  
Sprague Dawley Rats ◽  
New Treatments ◽  
Hypnagogic Hallucinations

Abstract Introduction Narcolepsy is characterized by sleep fragmentation, sleep paralysis, hypnagogic hallucinations and cataplexy. The cataplexy is a sudden loss of muscle tone triggered by emotions in humans, as well as in animal models. It is stablished that most of the patients had a significant decrease of orexin neurons in the lateral hypothalamus. Taiep rats had a mutation in tubulin TUBB4A and suffer immobility episodes (IE′s) that had a desynchronized activity in the cortex associated with theta rhythm in the hippocampus similar to narcolepsy patients. The aim of this study was to analyze the effects of central administration of an orexin B agonist and determination by immunohistochemistry of the number of orexin neurons on adult male taiep rats. Methods We used 14 male taiep rats of 9 months of age. The subjects (Ss) lived 3-4 in acrylic cages with water and food pellets ad libitum, under a 12:12 light-dark cycle (lights on at 0700), whit-controlled temperature and humidity in the recording room. All Ss were implanted to record EEG, EMG and EOG to characterize immobility episodes (IE′s) in a control 8 h recording and after i.c.v. administration of [Ala 11, D-Leu 15]-orexin B with 1, 3 and 10 nmol/1 μL. We measured the number, mean duration and latency to the first IE′s. Results The administration of [Ala 11, D-Leu 15]-orexin B significantly reduced the number of IE′s (P<0.01), from 4.28 ± 1.5 IE′s to just 0.25 ± 0.17 with 10 nmol/1 μL dose, but did not change the amount of awakening, slow wave or rapid eye movement sleep. Importantly, the number or orexins neurons were similar between taiep and Sprague-Dawley rats. Conclusion The myelin mutant taiep rats is a model of narcolepsy with cataplexy with normal number of orexin neurons in the lateral hypothalamus. Additionally, a specific orexin B agonist reduced IE′s without any effect the sleep pattern. This could be useful for the design of new treatments. Support CONACYT grants 243333 and 243247 to CC and JRE, respectively. Grants from VIEP-BUAP 2019 and CA in Neuroendocrinología BUAP-CA-288.

scholarly journals Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad

2018 ◽  
Vol 30 (5) ◽  
pp. 708-714 ◽  
Author(s):  
David C. Dorman ◽  
Melanie L. Foster ◽  
Brooke Olesnevich ◽  
Brad Bolon ◽  
Aude Castel ◽  
...  
Keyword(s):  
Motor Activity ◽  
Polyacrylic Acid ◽  
Muscle Tone ◽  
Clinical Signs ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Acute Neurotoxicity ◽  
Disposable Diapers

Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered “nontoxic” with acute oral median lethal doses (LD50) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6–19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.

Alterations in extracellular GABA in the ventral hypothalamus of rats in response to acute glucoprivation

1995 ◽  
Vol 269 (5) ◽  
pp. R1174-R1178 ◽  
Author(s):  
J. L. Beverly ◽  
M. F. Beverly ◽  
M. M. Meguid
Keyword(s):  
Lateral Hypothalamus ◽  
Ventromedial Hypothalamus ◽  
Ringer Solution ◽  
Sample Period ◽  
Sprague Dawley ◽  
Gaba Concentration ◽  
Sprague Dawley Rats ◽  
Access To Food ◽  
Glucose Status

gamma-Aminobutyric acidergic (GABA) mechanisms in the ventral hypothalamus may be involved in counterregulatory responses to glucoprivic episodes. Microdialysis probes (1 mm) were placed into the ventromedial hypothalamus (VMH) or lateral hypothalamus (LHA) of male Sprague-Dawley rats 3.5 h before 2-deoxy-D-glucose (2-DG) administration (200 mg/kg i.v.). Probes were perfused (2 ml/min) with Ringer solution, and samples were collected every 10 min from 30 min before to 60 min after 2-DG. By 30 min after 2-DG, GABA concentration in VMH dialysate increased in a bimodal fashion to 204 +/- 36% (P < 0.01) of baseline, and GABA concentration in LHA dialysate decreased to 77 +/- 4% (P < 0.01) of baseline. The changes in dialysate GABA concentrations occurred concurrently with the animals eating and returned to baseline by 60 min. When animals were denied access to food after 2-DG, the decrease in LHA GABA was not apparent and VMH GABA remained approximately 15% above baseline at the end of the sample period. The results of the present study provide evidence that GABAergic systems in the ventral hypothalamus are responsive to alterations in glucose status.

Central nervous system histamine regulates peripheral sympathetic activity

1991 ◽  
Vol 260 (1) ◽  
pp. H218-H224 ◽  
Author(s):  
V. F. Akins ◽  
S. L. Bealer
Keyword(s):  
Hypertonic Saline ◽  
Pressor Response ◽  
Plasma Concentrations ◽  
Central Administration ◽  
Sprague Dawley ◽  
Irreversible Inhibitor ◽  
Brain Histamine ◽  
Sprague Dawley Rats ◽  
H1 Antagonist ◽  
Peripheral Sympathetic Activity

Brain histamine (HA) was depleted in conscious Sprague-Dawley rats by central administration of alpha-fluoromethyl-histidine (alpha-FMH), an irreversible inhibitor of the HA synthesizing enzyme. Isotonic or hypertonic saline was infused intravenously at 10 microliters.100 g-1.min-1 for 30 min and mean arterial pressure (MAP) and heart rate (HR) were monitored. In addition, plasma vasopressin (AVP) and norepinephrine (NE) were measured pre- and postinfusion. Animals pretreated with alpha-FMH showed a delayed and attenuated pressor response and bradycardia during hypertonic saline (HTS) infusion and a significant reduction in plasma NE levels (-29 +/- 8% below control values). However, plasma concentrations of AVP were similar in both groups. Central pretreatment with the H1-antagonist pyrilamine (PYR) also delayed the onset and significantly attenuated the pressor response to HTS infusion, and caused dose-related decreases in plasma NE concentrations (-34 +/- 8, -47 +/- 5, and -52 +/- 7% after 60, 100, and 600 nmol PYR, respectively). These data indicate a role for central HA in peripheral sympathetic activation but not as a mediator of AVP release to a peripheral hyperosmotic stimulus.

Modulation of Rat Pial Arteriolar Responses to Flow by Glucose

2002 ◽  
Vol 97 (2) ◽  
pp. 471-477 ◽  
Author(s):  
Michael E. Ward ◽  
Lu Yan ◽  
Mark R. Angle
Keyword(s):  
Shear Stress ◽  
High Glucose ◽  
Glucose Concentration ◽  
Muscle Tone ◽  
Transmural Pressure ◽  
Intraluminal Pressure ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pial Arterioles ◽  
Physiologic Saline

Background Pial arteriolar responses to flow contribute to regulation of cerebral perfusion and vary according to the transmural pressure to which the vessel is exposed. This study determined the effect of increased glucose concentration on the flow responses of pial arterioles at low and high levels of transmural pressure. Methods Pial arterioles from Sprague-Dawley rats were mounted in a perfusion myograph. In some arterioles, the endothelium was removed by perfusion with air. Diameters were recorded at transmural pressures of 60 and 120 mmHg during superfusion with physiologic saline containing 5 mm D-glucose, 20 mm D-glucose, or 5 mm D-glucose and 15 mm L-glucose. Diameters during superfusion with saline containing 44 mm D-glucose were measured at an intraluminal pressure of 60 mmHg. Flow-diameter relationships (5-30 microl/min) were recorded during perfusion with the same solutions. Results Increasing D-glucose concentration caused constriction (P &lt; 0.05) in endothelium-denuded but not in endothelium-intact arterioles. Addition of L-glucose caused constriction in endothelium-intact and -denuded vessels (P &lt; 0.05 for both). At a D-glucose concentration of 5 mm and at low intraluminal pressure, flow elicits endothelium-dependent dilation such that shear stress remains constant. At a D-glucose concentration of 20 or 44 mm, after addition of L-glucose (15 mm), and at high intraluminal pressures, flow elicits constriction and shear stress is unregulated. Conclusions High glucose concentrations elicit increased basal arteriolar smooth muscle tone that is counteracted by release of endothelium-derived relaxing factors. Endothelium-dependent relaxation to flow (shear stress) is inhibited at high glucose concentrations.

Orexin-induced feeding requires NMDA receptor activation in the perifornical region of the lateral hypothalamus

2007 ◽  
Vol 293 (3) ◽  
pp. R1022-R1026 ◽  
Author(s):  
Dolores F. Doane ◽  
Marcus A. Lawson ◽  
Jonathan R. Meade ◽  
Catherine M. Kotz ◽  
J. Lee Beverly
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Lateral Hypothalamus ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Sprague Dawley ◽  
Orexin A ◽  
Sprague Dawley Rats ◽  
Artificial Cerebrospinal Fluid

Food intake is stimulated following administration of orexin-A into the perifornical region of the lateral hypothalamus (LH/PFA). Orexin neurons originating in the LH/PFA interact with a number of hypothalamic systems known to influence food intake, including glutamatergic neurons. Glutamatergic systems in the LH/PFA were demonstrated to initiate feeding through N-methyl-d-aspartic acid (NMDA) receptors. Male Sprague-Dawley rats fitted with brain guide cannulas to the LH/PFA were used in two experiments. In the first experiment, a combination microdialysis/microinjection probe was used to deliver artificial cerebrospinal fluid (aCSF) or 500 pmol of orexin-A into the LH/PFA. Orexin-A increased interstitial glutamate to 143 ± 12% of baseline ( P < 0.05), which remained elevated over the 120-min collection period. In the second experiment, the NMDA receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5; 10 nmol) was administered before orexin-A. The orexin-induced increase in food intake (from 1.1 ± 0.4 to 3.2 ± 0.5 g, P < 0.05) during the first hour was absent in rats receiving d-AP5 + orexin-A (1.2 ± 0.5 g). There was no effect of d-AP5 alone on food intake. These data support glutamatergic systems in the LH/PFA mediating the feeding response to orexin-A through NMDA receptors.

Evaluation of the immune response of male and female rats vaccinated with cDNA encoding a cysteine proteinase of Fasciola hepatica (FhPcW1)

2013 ◽  
Vol 58 (2) ◽  
Author(s):  
Agnieszka Wesołowska ◽  
Luke Norbury ◽  
Kamil Januszkiewicz ◽  
Luiza Jedlina ◽  
Sławomir Jaros ◽  
...  
Keyword(s):  
Fasciola Hepatica ◽  
Cysteine Proteinase ◽  
Female Rats ◽  
Parasitic Infections ◽  
Sprague Dawley ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
New Treatments ◽  
Humoral Responses ◽  
Gender Influences

AbstractNot only do males and females of many species vary in their responses to certain parasitic infections, but also to treatments such as vaccines. However, there are very few studies investigating differences among sexes following vaccination and infection. Here we demonstrate that female Sprague-Dawley rats vaccinated with cDNA encoding a recently discovered cysteine proteinase of Fasciola hepatica (FhPcW1) develop considerably lower liver fluke burdens after F. hepatica infection than their male counterparts. This is accompanied by differences in the course of their immune responses which involve different eosinophil and monocyte responses throughout the study as well as humoral responses. It is evident that host gender influences the outcome of parasitic infections after vaccination and research on both sexes should be considered when developing new treatments against parasites.

Noradrenergic and GABAergic systems in the medial hypothalamus are activated during hypoglycemia

2001 ◽  
Vol 280 (2) ◽  
pp. R563-R569 ◽  
Author(s):  
J. Lee Beverly ◽  
Martin G. De Vries ◽  
Stephan D. Bouman ◽  
Linda M. Arseneau
Keyword(s):  
Paraventricular Nucleus ◽  
Lateral Hypothalamus ◽  
Plasma Glucose ◽  
Ventromedial Nucleus ◽  
Insulin Administration ◽  
Sprague Dawley ◽  
Direct Response ◽  
Compensatory Mechanisms ◽  
Sprague Dawley Rats ◽  
Medial Hypothalamus

Noradrenergic and GABAergic systems in the medial hypothalamus influence plasma glucose and may be activated during glucoprivation. Microdialysis probes were placed into the ventromedial nucleus (VMH), lateral hypothalamus (LHA), and paraventricular nucleus (PVH) of male Sprague-Dawley rats to monitor extracellular concentrations of norepinephrine (NE) and GABA. During systemic hypoglycemia, induced by insulin (1.0 U/kg), NE concentrations increased in the VMH ( P < 0.05) and PVH ( P = 0.06) in a bimodal fashion during the first 10 min and 20–30 min after insulin administration. In the VMH, GABA concentrations increased ( P < 0.05) in a similar manner as NE. Extracellular NE concentrations in the LHA were slightly lower ( P = 0.13), and GABA levels remained at baseline. The increases in NE and GABA in the VMH were absent during euglycemic clamp; however, NE in the PVH still increased, reflecting a direct response to hyperinsulinemia. On the basis of these data, we propose that the activity of noradrenergic afferents to the medial hypothalamus is increased during hypoglycemia and influences the activity of local GABAergic systems to activate appropriate physiological compensatory mechanisms.

Cardiovascular and renal responses produced by central orphanin FQ/nociceptin occur independent of renal nerves

1999 ◽  
Vol 277 (4) ◽  
pp. R987-R995 ◽  
Author(s):  
Daniel R. Kapusta ◽  
Velga A. Kenigs
Keyword(s):  
Renal Hemodynamics ◽  
Renal Nerves ◽  
Central Administration ◽  
Orphanin Fq ◽  
Sprague Dawley ◽  
Renal Sympathetic Nerve Activity ◽  
Conscious Rats ◽  
Sprague Dawley Rats ◽  
Renal Responses

The present study investigated the role of the renal nerves in mediating the cardiovascular and renal responses produced by the central administration of the opioid-like peptide orphanin FQ/nociceptin (OFQ/N) in conscious Sprague-Dawley rats. In conscious rats, OFQ/N (10 μg icv) produced a transient bradycardia and hypotension (nadir 20 min). Although renal sympathetic nerve activity (RSNA) initially remained unchanged, a delayed renal sympathoinhibitory response occurred after recovery (30 min) of blood pressure. By 30 and 70 min postinjection, RSNA decreased to 75 and 66% of control, respectively. Coinciding with the decrease in RSNA, central OFQ/N elicited a diuresis and antinatriuresis that occurred independent of changes in renal hemodynamics. In other studies, intracerebroventricular OFQ/N produced similar cardiovascular and renal excretory responses in bilaterally renal-denervated rats. Finally, in conscious sinoaortic deafferentiated rats, intracerebroventricular OFQ/N produced a rapid decrease in RSNA (55% of control, 10 min; 38% of control, 20 min) that paralleled the onset of the hypotension and bradycardia. These studies demonstrate that in conscious rats, intracerebroventricular OFQ/N produces a centrally mediated inhibition of RSNA which, due to activation of baroreflex mechanisms, is temporally dissociated from the hypotensive and bradycardia responses. As revealed in renal-denervated rats, the cardiovascular and renal excretory responses produced by central OFQ/N occur by a pathway that is independent of intact renal nerves or changes in renal hemodynamics.

scholarly journals Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats

Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. 465-473 ◽  
Author(s):  
Zafer Sahin ◽  
Sinan Canpolat ◽  
Mete Ozcan ◽  
Tuba Ozgocer ◽  
Haluk Kelestimur
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Female Rats ◽  
Central Administration ◽  
Vaginal Opening ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Induced Changes ◽  
Lh Secretion

The aim of this study was to determine the modulatory effects of peptide 234 (p234) (an antagonist of GPR54 receptors) on kisspeptin and RF9 (an RFamide-related peptide antagonist)-induced changes in reproductive functions and energy balance in female rats. Female Sprague–Dawley rats were weaned on postnatal day (pnd) 21. The animals were intracerebroventricularly cannulated under general anesthesia on pnd 23. Groups of female rats were injected with kisspeptin, RF9, p234, kisspeptin plus p234, or RF9 plus p234, daily. The experiments were ended on the day of first diestrus following pnd 60. Kisspeptin or RF9 alone advanced vaginal opening (VO), which was delayed by administration of kisspeptin antagonist alone. In the rats given kisspeptin plus p234 or RF9 plus p234, VO was not different from control rats. Kisspeptin and RF9 elicited significant elevations in circulating LH levels. Coadministrations of kisspeptin or RF9 with p234 decreased LH levels significantly. The use of p234 alone did not cause any significant change in LH secretion. Kisspeptin decreased both food intake and body weight while RF9 decreased only food intake without affecting body weight. The effects of kisspeptin on energy balance were also reversed by central administration of p234. In conclusion, kisspeptin antagonist, p234, modulates the effects of kisspeptin on reproductive functions and energy balance, whereas RF9 seems to exert only its effects on reproductive functions by means of GPR54 signaling in female rats.

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