Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

2002 ◽  
Vol 93 (3) ◽  
pp. 936-946 ◽  
Author(s):  
Richard Kinkead ◽  
Olivier Belzile ◽  
Roumiana Gulemetova

To test the hypothesis that serotonin (5-hydroxytryptamine; 5-HT)-receptor activation elicits age-dependent changes in respiratory motor output, we compared the effects of 5-HT bath application (5-HT concentration = 0.5–25 μM) onto in vitro brain stem preparations from pre- and postmetamorphic bullfrog tadpoles. Recording of motor output related to gill and lung ventilation showed that 5-HT elicits a dose-dependent depression of gill burst frequency in both groups. In contrast, the lung burst frequency response was stage dependent; an increase in lung burst frequency at low 5-HT concentration (≤0.5 μM) was observed only in the postmetamorphic group. Higher 5-HT concentrations decreased lung burst frequency in all preparations. Gill burst frequency attenuation is mediated (at least in part) by 5-HT1A-receptor activation in an age-dependent fashion. We conclude that serotonergic modulation of respiratory motor output 1) changes during tadpole development and 2) is distinct for gill and lung ventilation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Luping Zhang ◽  
Dengyuan Zhou ◽  
Qiuyan Li ◽  
Shuo Zhu ◽  
Muhammad Imran ◽  
...  

Flaviviruses are the major emerging arthropod-borne pathogens globally. However, there is still no practical anti-flavivirus approach. Therefore, existing and emerging flaviviruses desperately need active broad-spectrum drugs. In the present study, the antiviral effect of steroidal dehydroepiandrosterone (DHEA) and 23 synthetic derivatives against flaviviruses such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), and Dengue virus (DENV) were appraised by examining the characteristics of virus infection both in vitro and in vivo. Our results revealed that AV1003, AV1004 and AV1017 were the most potent inhibitors of flavivirus propagation in cells. They mainly suppress the viral infection in the post-invasion stage in a dose-dependent manner. Furthermore, orally administered compound AV1004 protected mice from lethal JEV infection by increasing the survival rate and reducing the viral load in the brain of infected mice. These results indicate that the compound AV1004 might be a potential therapeutic drug against JEV infection. These DHEA derivatives may provide lead scaffolds for further design and synthesis of potential anti-flavivirus potential drugs.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ganiyu Oboh ◽  
Ayodele J. Akinyemi ◽  
Olasunkanmi S. Omojokun ◽  
Idowu S. Oyeleye

Background. Cola acuminataseed, a commonly used stimulant in Nigeria, has been reportedly used for the management of neurodegenerative diseases in folklore without scientific basis. This study sought to investigate the anticholinesterase and antioxidant properties of aqueous extracts fromC. acuminataseedin vitro.Methodology.The aqueous extract ofC. acuminataseed was prepared (w/v) and its effect on acetylcholinesterase (AChE) and butyrylcholinesterase activities, as well as some prooxidant (FeSO4, sodium nitroprusside (SNP), and quinolinic acid (QA)) induced lipid peroxidation in rat brainin vitro, was investigated.Results.The results revealed thatC. acuminataseed extract inhibited AChE (IC50= 14.6μg/mL) and BChE (IC50= 96.2μg/mL) activities in a dose-dependent manner. Furthermore, incubation of rat’s brain homogenates with some prooxidants caused a significant increaseP<0.05in the brain malondialdehyde (MDA) content and inhibited MDA production dose-dependently and also exhibited further antioxidant properties as typified by their high radicals scavenging and Fe2+chelating abilities.Conclusion.Inhibition of AChE and BChE activities has been the primary treatment method for mild Alzheimer’s disease (AD). Therefore, one possible mechanism through which the seed exerts its neuroprotective properties is by inhibiting cholinesterase activities as well as preventing oxidative-stress-induced neurodegeneration. However, this is a preliminary study with possible physiological implications.


2006 ◽  
Vol 290 (6) ◽  
pp. R1537-R1541 ◽  
Author(s):  
Kiyoshi Tsukamoto ◽  
Yukiomi Nakade ◽  
Christopher Mantyh ◽  
Kirk Ludwig ◽  
Theodore N. Pappas ◽  
...  

Corticotropin releasing factor (CRF) is one of the most important factors in the mechanism of stress-induced stimulation of colonic motility. However, it is controversial whether stress-induced stimulation of colonic motility is mediated via central or peripheral CRF receptors. We investigated the hypothesis that peripherally injected CRF accelerates colonic motility through the central CRF receptor, but not the peripheral CRF receptor. A strain gauge transducer was sutured on the serosal surface of the proximal colon. Colonic motility was monitored before and after the peripheral injection of CRF. An in vitro muscle strip study was also performed to investigate the peripheral effects of CRF. Subcutaneous injection of CRF (30–100 μg/kg) stimulated colonic motility in a dose-dependent manner. The stimulatory effect of peripherally administered CRF on colonic motility was abolished by truncal vagotomy, hexamethonium, atropine, and intracisternal injection of astressin (a CRF receptor antagonist). No responses to CRF (10−9 −10−7 M) of the muscle strips of the proximal colon were observed. These results suggest that the stimulatory effect of colonic motility in response to peripheral administration of CRF is mediated by the vagus nerve, nicotinic receptors, muscarinic receptors, and CRF receptors of the brain stem. It is concluded that peripherally administered CRF reaches the area postrema and activates the dorsal nucleus of vagi via central CRF receptors, resulting in stimulation of the vagal efferent and cholinergic transmission of the proximal colon.


1995 ◽  
Vol 268 (1) ◽  
pp. R21-R27 ◽  
Author(s):  
H. Matsui ◽  
S. Aou ◽  
J. Ma ◽  
T. Hori

The central actions of parathyroid hormone (PTH) on the blood ionized calcium level in anesthetized rats and the neuronal activity of the ventromedial nucleus of the hypothalamus (VMH) in vitro were investigated. An intracerebroventricular injection of PTH (0.01, 0.1, and 1 microgram) prevented urethan-induced hypocalcemia in a dose-dependent manner, whereas either an intravenous or an intracisternal injection of PTH (1 microgram) was ineffective. Eighty-three of 177 VMH neurons responded to a bath application of PTH (10(-7) or 3 x 10(-7) M): a majority (72, 83%) of the responsive cells decreased, whereas 11 increased their activity. This inhibitory effect of PTH on neuronal activity still persisted after synaptic blocking in a Ca(2+)-free/high-Mg2+ medium. A PTH receptor antagonist, [Tyr34]bPTH-(7-34)-NH2, suppressed the effect of PTH on the neuronal activity. These findings thus suggest that brain PTH has a calciotropic function and that one of the possible target sites is the VMH, where PTH inhibits its neuronal activity through a postsynaptic mechanism mediated by PTH receptors.


1997 ◽  
Vol 17 (5) ◽  
pp. 567-570 ◽  
Author(s):  
Tor S. Haugstad ◽  
Iver A. Langmoen

The effect of the glutamate analogue L- α-aminoadipate ( αAA) on the release of glutamate and γ-aminobutyric acid (GABA) from rat hippocampal slices was investigated in vitro. Oxygen/glucose deprivation caused a large release of glutamate and GABA. αAA added during energy deprivation reduced the glutamate release in a dose-dependent manner (56% reduction at 5 m M), whereas GABA release was unchanged. We speculate that ischemic glutamate release from the brain is mediated by a low affinity transport mechanism that is blocked by αAA.


1984 ◽  
Vol 107 (3) ◽  
pp. 395-400 ◽  
Author(s):  
Itaru Kojima ◽  
Etsuro Ogata ◽  
Hiroshi Inano ◽  
Bun-ichi Tamaoki

Abstract. Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000. SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H ]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.


This trial research was performed to discuss the immune-influence of Melaleuca leucadendra ‘paper-bark tree’ dried leaves which is an important medical plant known in many regions in the world. The leaves were dissolved in a mixture of (ethanol + water) (3:1) mixture, then filtered, evaporated and dried under reduced pressure to obtain leaves extract. The macrophages of blood derived origin were provided from rats and mixed with three different leaves extracts doses in tissue culture plates and incubated then stained with fluorescent acridine orange and examined under fluorescent microscope to assess the phagocytic and killing potency. The wells contents were aspirated and assayed for nitric oxide and interleukin-2 levels. The results displayed an obvious increase in phagocytic, killing performance as well as nitric oxide and IL-2 level production than control in a dose dependent manner. The obtained results suggested the immune-stimulant impact of the paper-bark tree leaves.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin N. Nelson ◽  
Savannah G. Beakley ◽  
Sierra Posey ◽  
Brittney Conn ◽  
Emma Maritz ◽  
...  

AbstractCryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.


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