scholarly journals Do Stereoisomers of Homocysteic Acid Exhibit Different Convulsant Action in Immature Rats?

2019 ◽  
pp. S361-S366
Author(s):  
P. MAREŠ ◽  
J. FOLBERGROVÁ ◽  
R. HAUGVICOVÁ ◽  
H. KUBOVÁ
Keyword(s):  
Nmda Receptors ◽  
Ampa Receptors ◽  
Dominant Role ◽  
Qualitative Difference ◽  
Homocysteic Acid ◽  
Immature Rats ◽  
Old Rats ◽  
Clonic Seizures

Mechanism of ictogenesis of D- and L-stereroisomers of homocysteic acid was studied in 12-day-old rats by means of antagonists of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. There was no qualitative difference between the two stereoisomers in generation of emprosthotonic (flexion) as well as generalized tonic-clonic seizures. Moderate differences were observed in the first, nonconvulsive effects of the two isomers. As generation of the two types of seizures is concerned, NMDA and AMPA participate in generalized tonic-clonic seizures whereas NMDA receptors play a dominant role in generation of flexion seizures.

scholarly journals Anticonvulsant Action of a New Analogue of Allopregnanolone in Immature Rats

2010 ◽  
pp. 305-308
Author(s):  
P Mareš ◽  
H Kubová ◽  
A Kasal
Keyword(s):  
Clinical Trials ◽  
Acute Treatment ◽  
Age Groups ◽  
Neuroactive Steroid ◽  
Reference Drug ◽  
Anticonvulsant Action ◽  
Immature Rats ◽  
Effective Doses ◽  
Old Rats ◽  
Clonic Seizures

Neuroactive steroids represent potential antiepileptic drugs. We tested a newly synthesized analogue of allopregnanolone 3αhydroxy-21ξ,22-oxido-21-homo-5α-pregnan-20-on (HOHP) against two types of pentylenetetrazol-induced seizures (100 mg/kg s.c.) in 12- and 25-day-old rats. Ganaxolone, a neuroactive steroid in clinical trials, served as a reference drug. Pretreatment with either steroid suppressed generalized tonicclonic seizures in both age groups, their efficacy was comparable. HOHP as well as ganaxolone were more active in 12- than in 25-day-old rats (effective doses were 40 and 60 mg/kg, respectively). Minimal clonic seizures, which can be elicited only in 25-day-old rats, were not influenced by any drug. Very short duration of anticonvulsant action of HPOP demonstrated in 12-day-old animals indicates that this drug might be used only in acute treatment in epileptology.

THE ROLE OF THE MOTHER IN 131I METABOLISM OF SUCKING AND WEANLING RATS

1965 ◽  
Vol 43 (3) ◽  
pp. 431-436 ◽  
Author(s):  
M. Samel ◽  
A. Caputa
Keyword(s):  
Urinary Bladder ◽  
In Utero ◽  
The State ◽  
Newborn Rats ◽  
Weanling Rats ◽  
Immature Rats ◽  
Other Substances ◽  
Old Rats

In newborn rats the mother provokes the emptying of the urinary bladder by stimulating the perineum with her tongue. The possibility that mothers may thereby ingest the urine of their young has been studied by means of 131I on nine litters of rats aged 10 to 29 days. The results indicate that a considerable quantity of 131I administered intraperitoneally to 10- and 18-day-old rats, which were then reunited with their mothers for 4 hours, reappears in the organism of uninjected nurslings after passing through the organism of the mother. The amount of 131I transferred from injected rats into the bodies of isolated uninjected rats of the same litter decreased during the period of weaning. The observed recirculation of 131I between immature rats and their mothers in both directions may represent a saving mechanism which might include several other substances and would compensate for their loss via the milk, and suggests a new aspect of maternal–neonatal interrelationship which appears as a continuation of the state existing in utero.

scholarly journals Control of AMPA receptor activity by the extracellular loops of auxiliary proteins

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Irene Riva ◽  
Clarissa Eibl ◽  
Rudolf Volkmer ◽  
Anna L Carbone ◽  
Andrew JR Plested
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
De Novo ◽  
Dominant Role ◽  
Mammalian Brain ◽  
Binding Assays ◽  
Receptor Kinetics ◽  
Receptor Complexes ◽  
Extracellular Loops ◽  
Kinetics Of

At synapses throughout the mammalian brain, AMPA receptors form complexes with auxiliary proteins, including TARPs. However, how TARPs modulate AMPA receptor gating remains poorly understood. We built structural models of TARP-AMPA receptor complexes for TARPs γ2 and γ8, combining recent structural studies and de novo structure predictions. These models, combined with peptide binding assays, provide evidence for multiple interactions between GluA2 and variable extracellular loops of TARPs. Substitutions and deletions of these loops had surprisingly rich effects on the kinetics of glutamate-activated currents, without any effect on assembly. Critically, by altering the two interacting loops of γ2 and γ8, we could entirely remove all allosteric modulation of GluA2, without affecting formation of AMPA receptor-TARP complexes. Likewise, substitutions in the linker domains of GluA2 completely removed any effect of γ2 on receptor kinetics, indicating a dominant role for this previously overlooked site proximal to the AMPA receptor channel gate.

scholarly journals Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs

2011 ◽  
Vol 4 (1) ◽  
pp. 30 ◽  
Author(s):  
Thomas M Sanderson ◽  
Graham L Collingridge ◽  
Stephen M Fitzjohn
Keyword(s):  
Nmda Receptors ◽  
Ampa Receptors

scholarly journals ENGLISH VERSION: AGE FEATURES OF RADIOACTIVE IODINE (131I) ABSORPTION BY RAT THYROID GLANDS IN CORRECTION OF THE DIETARY IODINE DEFICIENCY WITH ORGANIC IODINE

2021 ◽  
Vol 25 (1-2) ◽  
pp. 31-35
Author(s):  
O.I. Ryabukha
Keyword(s):  
Thyroid Gland ◽  
Iodine Deficiency ◽  
Radioactive Iodine ◽  
Male Rats ◽  
Organic Iodine ◽  
Study Results ◽  
Thyroid Glands ◽  
Immature Rats ◽  
Old Rats ◽  
Rat Thyroid

The structure of endocrine morbidity is characterized by a significant spread of thyroid pathology. The insufficient efficacy of inorganic iodine drugs poses the problem of search for new means for iodine deficiency treatment and prevention. Given the progressive aging of the population in economically developed countries, the purpose of the study was to clarify the effect of organic iodine on the features of absorption and elimination of radioactive iodine from the thyroid glands of variously aged rats in the conditions of iodine deficiency in the diet. The study was performed on nonlinear white male rats in two series of studies that were kept on iodine-deficient isocaloric starch-casein diet for 60 days: the first series included two groups of old rats weighing 0.400-0.450 kg, the second series – two groups of sexually immature rats weighing 0.060-0.090 kg. There were 5 rats in each group. In animals of the experimental groups in each series, 10% of casein in the diet was replaced with organic iodine, which came with iodine-protein preparation from the red Black Sea algae Phyllophora nervosa. The functional state of the thyroid gland was studied using the Sodium Iodide Na 131 I Injection drug. The dosimetry was performed using the STS-6 Geiger-Muller Detector. Radioindication of the thyroid gland was carried out after subcutaneous administration of 0.1 ml of 131I solution at the following time intervals: 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours after administration of 131I. The study results were presented as a percentage of the radioiodine dose administered, adjusted for natural radioactivity background and the radioactive decay of the drug. It was found that in the iodine deficiency conditions, the thyroid glands of old rats have higher rates of radioiodine absorption and a lower rate of its excretion than the glands of immature rats, which indicates their lower iodine reserve and greater liability to iodine deficiency pathology. Intake of organic iodine regardless of the rats’ age is accompanied by a decrease in radioiodine accumulation and acceleration of its excretion from the thyroid gland, which indicates a decrease in functional stress, but the glands of older rats absorb more iodine and excrete it more slowly, indicating less effective correction of iodine deficiency with age. Reduced functional activity of the thyroid glands in old rats can be used as a sensitive changes marker for the in-depth study of thyrotropic and thyroid disrupting effects.

scholarly journals Determining the Activation Time Course of Synaptic AMPA Receptors from Openings of Colocalized NMDA Receptors

1999 ◽  
Vol 77 (3) ◽  
pp. 1418-1427 ◽  
Author(s):  
Ingo C. Kleppe ◽  
Hugh P.C. Robinson
Keyword(s):  
Nmda Receptors ◽  
Ampa Receptors ◽  
Time Course ◽  
Activation Time

Interaction of Dopamine D1 and NMDA Receptors Mediates Acute Clozapine Potentiation of Glutamate EPSPs in Rat Prefrontal Cortex

2002 ◽  
Vol 87 (5) ◽  
pp. 2324-2336 ◽  
Author(s):  
Long Chen ◽  
Charles R. Yang
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Ampa Receptors ◽  
Nmda Receptor Antagonist ◽  
D1 Receptor ◽  
Resting Membrane Potential ◽  
Cellular Mechanisms ◽  
Cognitive Improvement

The atypical antipsychotic drug clozapine effectively alleviates both negative and positive symptoms of schizophrenia via unclear cellular mechanisms. Clozapine may modulate both glutamatergic and dopaminergic transmission in the prefrontal cortex (PFC) to achieve part of its therapeutic actions. Using whole cell patch-clamp techniques, current-clamp recordings in layers V–VI pyramidal neurons from rat PFC slices showed that stimulation of local afferents (in 2 μM bicuculline) evoked mixed [AMPA/kainate and N-methyl-d-aspartate (NMDA) receptors] glutamate receptor-mediated excitatory postsynaptic potentials (EPSPs). Clozapine (1 μM) potentiated polysynaptically mediated evoked EPSPs ( V Hold = −65 mV), or reversed EPSPs (rEPSP, V Hold = +20 mV) for >30 min. The potentiated EPSPs or rEPSPs were attenuated by elevating [Ca2+]O(7 mM), by application of NMDA receptor antagonist 2-amino5-phosphonovaleric acid (50 μM), or by pretreatment with dopamine D1/D5 receptor antagonist SCH23390 (1 μM) but could be further enhanced by a dopamine reuptake inhibitor bupropion (1 μM). Clozapine had no significant effect on pharmacologically isolated evoked NMDA-rEPSP or AMPA-rEPSPs but increased spontaneous EPSPs without changing the steady-state resting membrane potential. Under voltage clamp, clozapine (1 μM) enhanced the frequency, and the number of low-amplitude (5–10 pA) AMPA receptor-mediated spontaneous EPSCs, while there was no such changes with the mini-EPSCs (in 1 μM TTX). Taken together these data suggest that acute clozapine can increase spike-dependent presynaptic release of glutamate and dopamine. The glutamate stimulates distal dendritic AMPA receptors to increase spontaneous EPSCs and enabled a voltage-dependent activation of neuronal NMDA receptors. The dopamine released stimulates postsynaptic D1 receptor to modulate a lasting potentiation of the NMDA receptor component of the glutamatergic synaptic responses in the PFC neuronal network. This sequence of early synaptic events induced by acute clozapine may comprise part of the activity that leads to later cognitive improvement in schizophrenia.

scholarly journals Ventilatory responses to ozone are reduced in immature rats

2000 ◽  
Vol 88 (6) ◽  
pp. 2023-2030 ◽  
Author(s):  
S. A. Shore ◽  
J. H. Abraham ◽  
I. N. Schwartzman ◽  
G. G. Krishna Murthy ◽  
J. D. Laporte
Keyword(s):  
Bronchoalveolar Lavage ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Ventilatory Responses ◽  
Sprague Dawley Rats ◽  
Immature Rats ◽  
Old Rats ◽  
Induced Changes

During ozone (O3) exposure, adult rats decrease their minute ventilation (V˙e). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O3(2 ppm) in nose-only-exposure plethysmographs. BaselineV˙e normalized for body weight decreased with age from 2.1 ± 0.1 ml ⋅ min−1⋅ g−1in 2-wk-old rats to 0.72 ± 0.03 ml ⋅ min−1⋅ g−1in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O3caused 40–50% decreases in V˙e that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O3-induced changes inV˙e were significantly less, and in 2- and 4-wk-old rats, no significant changes inV˙e were observed during O3exposure. The increased baseline V˙e and the smaller decrements in V˙e induced by O3in the immature rats imply that their delivered dose of O3is much higher than in adult rats. To determine whether these differences in O3dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O3was significantly greater in 2- than in 8-wk-old rats (267 ± 47 vs. 165 ± 22%, respectively, P < 0.05). O3exposure also caused a significant increase in PGE2in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O3is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.

Glutamate Controls the Induction of GABA-Mediated Giant Depolarizing Potentials Through AMPA Receptors in Neonatal Rat Hippocampal Slices

1999 ◽  
Vol 81 (5) ◽  
pp. 2095-2102 ◽  
Author(s):  
Sonia Bolea ◽  
Elena Avignone ◽  
Nicola Berretta ◽  
Juan V. Sanchez-Andres ◽  
Enrico Cherubini
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Neonatal Rat ◽  
Bath Application ◽  
Old Rats ◽  
Ca3 Pyramidal Cells ◽  
Recurrent Collaterals ◽  
Local Release

Glutamate controls the induction of GABA-mediated giant depolarizing potentials through AMPA receptors in neonatal rat hippocampal slices. Giant depolarizing potentials (GDPs) are generated by the interplay of the depolarizing action of GABA and glutamate. In this study, single and dual whole cell recordings (in current-clamp configuration) were performed from CA3 pyramidal cells in hippocampal slices obtained from postnatal (P) days P1- to P6-old rats to evaluate the role of ionotropic glutamate receptors in GDP generation. Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10–40 μM) completely blocked GDPs. However, in the presence of CNQX, it was still possible to re-induce the appearance of GDPs with GABA (20 μM) or (RS)-α-amino-3-hydroxy-5-methyl-4-isoxadepropionate (AMPA) (5 μM). This effect was prevented by the more potent and selective AMPA receptor antagonist GYKI 53655 (50–100 μM). In the presence of GYKI 53655, both kainic or domoic acid (0.1–1 μM) were unable to induce GDPs. In contrast, bath application of d-(−)-2-amino-5-phosphonopentanoic acid (50 μM) or (+)-3-(2carboxy-piperazin-4-yl)-propyl-l-phosphonic acid (20 μM) produced only a 37 ± 9% (SE) and 36 ± 11% reduction in GDPs frequency, respectively. Cyclothiazide, a selective blocker of AMPA receptor desensitization, increased GDP frequency by 76 ± 14%. Experiments were also performed with an intracellular solution containing KF to block GABAAreceptor-mediated responses. In these conditions, a glutamatergic component of GDP was revealed. GDPs could still be recorded synchronous with those detected simultaneously with KCl-filled electrodes, although their amplitude was smaller. Similar results were found in pair recordings obtained from minislices containing only a small portion of the CA3 area. These data suggest that GDP generation requires activation of AMPA receptors by local release of glutamate from recurrent collaterals.

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