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CA3 biochemical action

Lia Tsverava, Tamar Lordkipanidze, Eka Lepsveridze, Maia Nozadze, Marina Kikvidze, Revaz Solomonia
Identification of compounds preventing or modifying the biochemical changes that underlie the epileptogenesis process and understanding the mechanism of their action are of great importance. We have previously shown that myoinositol (MI) daily treatment for 28 days prevents certain biochemical changes that are triggered by kainic acid (KA) induced status epilepticus (SE). However in these studies we have not detected any effects of MI on the first day after SE. In the present study we broadened our research and focused on other molecular and morphological changes at the early stages of SE induced by KA and effects of MI treatment on these changes...
2016: BioMed Research International
José Christian Machado Ximenes, Kelly Rose Tavares Neves, Luzia Kalyne A M Leal, Marta Regina Santos do Carmo, Gerly Anne de Castro Brito, Maria da Graça Naffah-Mazzacoratti, Ésper Abrão Cavalheiro, Glauce Socorro de Barros Viana
Parkinson's disease is a neurodegenerative disorder where the main hallmark is the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive decline. Although current therapies focus on the restoration of dopamine levels in the striatum, prevention or disease-modifying therapies are urgently needed. Valproic acid (VA) is a wide spectrum antiepileptic drug, exerting many biochemical and physiological effects. It has been shown to inhibit histone deacetylase which seems to be associated with the drug neuroprotective action...
2015: Journal of Neurodegenerative Diseases
Joanna Chwiej, Agnieszka Skoczen, Katarzyna Matusiak, Krzysztof Janeczko, Agnieszka Patulska, Christophe Sandt, Rolf Simon, Malgorzata Ciarach, Zuzanna Setkowicz
A growing body of evidence demonstrates that dietary therapies, mainly the ketogenic diet, may be highly effective in the reduction of epileptic seizures. All of them share the common characteristic of restricting carbohydrate intake to shift the predominant caloric source of the diet to fat. Catabolism of fats results in the production of ketone bodies which become alternate energy substrates to glucose. Although many mechanisms by which ketone bodies yield its anticonvulsant effect are proposed, the relationships between the brain metabolism of the ketone bodies and their neuroprotective and antiepileptogenic action still remain to be discerned...
August 2015: Epilepsy & Behavior: E&B
Pishan Chang, Kate E Chandler, Robin S B Williams, Matthew C Walker
PURPOSE: Valproic acid (VPA) is widely used clinically in epilepsy, bipolar disorder, and migraine. In experimental models, it has also been shown to have neuroprotective and antiepileptogenic effects. Its mechanisms of action in these diverse conditions are, however, unclear, but there is some evidence indicating an effect of VPA upon protein kinase A (PKA) activity. We, therefore, asked whether VPA modulates cyclic adenosine monophosphate (cAMP)/PKA-dependent synaptic plasticity and whether this mode of action could explain its anticonvulsant effect...
August 2010: Epilepsia
Gustavo A Patino, Lieve R F Claes, Luis F Lopez-Santiago, Emily A Slat, Raja S R Dondeti, Chunling Chen, Heather A O'Malley, Charles B B Gray, Haruko Miyazaki, Nobuyuki Nukina, Fumitaka Oyama, Peter De Jonghe, Lori L Isom
Dravet syndrome (also called severe myoclonic epilepsy of infancy) is one of the most severe forms of childhood epilepsy. Most patients have heterozygous mutations in SCN1A, encoding voltage-gated sodium channel Na(v)1.1 alpha subunits. Sodium channels are modulated by beta1 subunits, encoded by SCN1B, a gene also linked to epilepsy. Here we report the first patient with Dravet syndrome associated with a recessive mutation in SCN1B (p.R125C). Biochemical characterization of p.R125C in a heterologous system demonstrated little to no cell surface expression despite normal total cellular expression...
August 26, 2009: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Pallavi Sethi, Amar Jyoti, Rameshwar Singh, Ejaz Hussain, Deepak Sharma
Aluminium (Al) is the most abundant metal known for its neurotoxicity in humans. It gains easy access to the central nervous system under normal physiological conditions and accumulates in different brain regions. It has been reported to be involved in the etiology of several neurodegenerative diseases. In this study, we have investigated the effects of long-term intake of aluminium chloride (AlCl(3)) on the electrophysiological, behavioral, biochemical and histochemical functions of hippocampus. Wistar rats were fed with AlCl(3) at a dose of 50mg/(kgday) for 6 months in the drinking water...
November 2008: Neurotoxicology
Kenneth A Pelkey, Chris J McBain
Individual axons of central neurons innervate a large number of distinct postsynaptic targets belonging to divergent functional categories such as glutamatergic principal cells and inhibitory interneurons. While each bouton along a common axon should experience the same activity pattern in response to action potential firing within the parent presynaptic neuron, accumulating evidence suggests that neighbouring boutons contacting functionally distinct postsynaptic targets regulate their release properties independently, despite being separated by only a few microns...
March 15, 2008: Journal of Physiology
Tyson B Brust, Francisco S Cayabyab, Ning Zhou, Brian A MacVicar
Adenosine is arguably the most potent and widespread presynaptic modulator in the CNS, yet adenosine receptor signal transduction pathways remain unresolved. Here, we demonstrate a novel mechanism in which adenosine A1 receptor stimulation leads to p38 mitogen-activated protein kinase (MAPK) activation and contributes to the inhibition of synaptic transmission. Western blot analysis indicated that selective A1 receptor activation [with N6-cyclopentyladenosine (CPA)] resulted in rapid increases in phosphorylated p38 (phospho-p38) MAPK immunoreactivity in membrane fractions, and decreases in phospho-p38 MAPK in cytosolic fractions...
November 29, 2006: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Arnaud Ruiz, Shankar Sachidhanandam, Jo Kristian Utvik, Françoise Coussen, Christophe Mulle
Heteromeric kainate receptors (KARs) containing both glutamate receptor 6 (GluR6) and KA2 subunits are involved in KAR-mediated EPSCs at mossy fiber synapses in CA3 pyramidal cells. We report that endogenous glutamate, by activating KARs, reversibly inhibits the slow Ca2+-activated K+ current I(sAHP) and increases neuronal excitability through a G-protein-coupled mechanism. Using KAR knockout mice, we show that KA2 is essential for the inhibition of I(sAHP) in CA3 pyramidal cells by low nanomolar concentrations of kainate, in addition to GluR6...
December 14, 2005: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
D-E Sok, S H Oh, Y-B Kim, H-G Kang, M R Kim
BACKGROUND: Reactive oxygen radicals have been implicated in the pathophysiology of many neurologic disorders and brain dysfunctions. Kainic acid has been used as a model agent for the study of neurotoxicity of various excitatory amino acids, since it induces neuronal damage through excessive production of reactive oxygen species. Petasites japonicus MAX (butterbur), cultivated as culinary vegetables in Eastern Asia, contains various kinds of phenolic compounds as well as sesquiterpenes, such as petasin...
March 2006: European Journal of Nutrition
Laura Lee Colgin, Don Kubota, Yousheng Jia, Christopher S Rex, Gary Lynch
Sharp waves (SPWs) occur in the hippocampal EEG during behaviours such as alert immobility and slow-wave sleep. Despite their widespread occurrence across brain regions and mammalian species, the functional importance of SPWs remains unknown. Experiments in the present study indicate that long-term potentiation (LTP) is significantly impaired in slices, prepared from the temporal aspect of rat hippocampus, that spontaneously generate SPW activity. This was probably not due to anatomical and/or biochemical abnormalities in temporal slices because stable LTP was uncovered in field CA1 when SPWs were eliminated by severing the projection from CA3...
August 1, 2004: Journal of Physiology
D X Tan, L C Manchester, R J Reiter, W Qi, S J Kim, G H El-Sokkary
In this investigation, 40 mg/kg of the excitatory neurotoxin kainic acid (KA) was subcutaneously administered to CD2-F1 mice. In this mouse strain morphological damage induced by KA in the hippocampus was markedly concentrated in the CA3 pyramidal neurons. Neuronal injury was accompanied by several pathological neurobehavioral activities including arching of tail, tremors and seizures, and by certain biochemical changes, i.e., increased lipid peroxidation products (LPO) in the brain. When melatonin was injected intraperitoneally at a single dose of 5 mg/kg 10 min before KA administration, it significantly reduced these pathological neurobehavioral changes and almost completely attenuated the increase in LPO and morphological damage induced by KA...
November 1, 1998: Journal of Neuroscience Research
X M Gao, C A Tamminga
Considerable research has identified a variety of acute PCP-induced biochemical changes in brain; but, little study has been devoted to characterizing delayed PCP-induced actions. These could potentially be associated with the prolonged psychotomimetic effects of the drug in humans. Here we studied delayed PCP-induced alterations in glutamate receptor subtype binding across a range of PCP doses, based on our previous findings of delayed regional cerebral metabolism changes with PCP. We report that 24 h after a single dose, PCP increases N-methyl-D-aspartate (NMDA)-sensitive [3H]glutamate binding in hippocampus (CA1) in an apparent dose-sensitive manner; no other dose-sensitive regional changes in NMDA binding sites were apparent in a sampling of 19 brain regions...
June 20, 1994: Neuroscience Letters
P D Suzdak, J A Jansen
We review the neurochemical and behavioral profile of the selective gamma-aminobutyric acid (GABA) uptake inhibitor, (R)-N-(4,4-di-(3-methylthien-2-yl)but-3-enyl) nipecotic acid hydrochloride [tiagabine (TGB), previously termed NNC 05-0328, NO 05-0328, and NO-328], which is currently in phase III clinical trials for epilepsy. TGB is a potent, and specific GABA uptake inhibitor. TGB lacks significant affinity for other neurotransmitter receptor binding sites and/or uptake sites. In electrophysiological experiments in hippocampal slices in culture, TGB prolonged the inhibitory postsynaptic potentials (IPSP) and inhibitory postsynaptic currents (IPSC) in the CA1 and CA3 produced by the addition of exogenous GABA...
June 1995: Epilepsia
J Andrä, H Luppa, J Weiss
This report describes the ultrastructural localization of the non-specific esterases in the pyramidal cells of the CA3-region of rat hippocampus. The use of specific inhibitors allowed the differentiation between aryl-, carboxyl- and acetylesterases. The thiolacetic acid reaction at pH = 5.2 and 7.0 proved to be a favourable method for the conditions of the hippocampus. Liver tissue served for control purposes. In the pyramidal cells carboxylesterase could be demonstrated on membranes and cisternes of the endoplasmic reticulum on polysomes and in the nuclear envelope...
1982: Acta Histochemica
S Sawada, M Higashima, C Yamamoto
Actions of dihydrokainate (DHKA) and 3-hydroxy-DL-aspartate (HAsp), inhibitors of high-affinity uptake for L-glutamate (Glu), were studied in vitro in thin hippocampal slices of the guinea pig. The amplitude of the depolarizations induced by Glu and by L-aspartate (Asp) in CA3 neurons are markedly augmented by DHKA and HAsp. Depolarizations induced by D-homocysteate (DH) were unaffected by the inhibitors. In about half of the neurons, depolarizations induced by L-homocysteate (LH) and by quisqualate (Quis) were slightly augmented by the inhibitors...
1985: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
J W Swann, R J Brady, D L Martin
Developmental alterations in GABAergic synaptic transmission were examined physiologically and biochemically in hippocampus of rats from 3 days of age to adulthood. Neither antidromic nor orthodromic stimulation could elicit identifiable inhibitory postsynaptic potentials in CA1 neurons in slices from rats 5 or 6 days of age. In contrast, at this age these stimuli result in large inhibitory postsynaptic potentials in CA3 pyramidal cells. In the latter cells orthodromic stimulation produced a brief monosynaptic excitatory postsynaptic potential which was followed by a large prolonged biphasic hyperpolarization...
1989: Neuroscience
S Oleskevich, L Descarries, J C Lacaille
A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals (axonal varicosities) in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region...
November 1989: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
S Bullock, B Lössner, M Krug, S Frey, S P Rose, H Matthies
411B is a monoclonal antibody raised to chick forebrain postsynaptic densities (PSDs) which also recognises an antigen in brain tissue from adult Wistar rats but not liver, heart, or lung. This antigen is enriched in the PSD fraction and appears to be a useful biochemical marker for plastic changes of postsynaptic structures in the rat brain. The aim of this study was to investigate whether 411B immunoreactivity is changed in various hippocampal subregions by post-tetanic long-term potentiation (LTP). LTP was elicited in freely moving rats by applying four trains of 300 square-wave pulses (frequency 200 Hz, pulse duration 0...
August 1990: Journal of Neurochemistry
M Ebadi, L C Murrin, R F Pfeiffer
The hippocampus, a component of the limbic system, is a prominent subcortical structure, which not only contains high concentrations of zinc, but also exhibits regional variations in this essential element, with concentrations being highest in the hilar region and lowest in the fimbria. For example, the concentration of zinc in the mossy fiber axons has been estimated to approach 300-350 microM. Both zinc and pyridoxal phosphate (PLP) deficiency and excess have been reported to produce epileptiform seizures, which are blocked by gamma-aminobutyric acid (GABA)...
1990: Annals of the New York Academy of Sciences
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