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Chemical Compound Review

Oriens     (4aS,6aS,6bR,12aS,14bS)-10- acetyloxy-2,4a...

Synonyms: AC1L4PSZ, LS-98288, UNII-85RP28F39U, EINECS 249-815-5, 6277-14-1 (Parent), ...
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Disease relevance of (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid

  • Our data establish a novel discovery that transient (10 min) global forebrain ischemia followed by reperfusion induces at least two distinct phases of fodrin proteolysis in hippocampus: an early phase in molecular layer and in stratum oriens of CA3 and CA1 sectors within 15 min and a late drastic and persistent phase in the entire CA1 after 4-24 h [1].
  • At 4 h during pilocarpine-induced status epilepticus (DPISE) in rat, protein kinase C (PKC)beta1, PKCbeta2, and PKCgamma were induced at the border between the stratum oriens and alveus (O/A border) of CA1 in the hippocampus [2].
  • Significant LTP of the late apical sink was found following a high intensity tetanus of stratum oriens (155 +/- 15%, n = 7), but no significant change of the late basal sink was found following tetanization of stratum radiatum (118 +/- 20%, n = 6) [3].
  • Pertussis toxin prevents induction of hippocampal long-term potentiation in the stratum radiatum and stratum oriens inputs to CA1 neurons [4].
  • A colocalization study in stratum oriens and pyramidale on the stimulated side of kindled animals 31 days after the last generalized seizure showed neither a reduction in the number of PV-immunoreactive somata nor in the number of GABA-immunopositive cell bodies that co-localized with PV [5].

Psychiatry related information on (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid

  • Alzheimer-related tau-pathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia [6].
  • The ongoing micro-electroencephalogram was recorded with a chronically implanted comb-like array of 16 tungsten semi-microelectrodes 0.2 or 0.25 mm apart, spanning CA1 strata oriens, pyramidale and radiatum and into subiculum, in four behavioral states: walking, standing still, paradoxical and slow wave sleep and under scopolamine [7].

High impact information on (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid

  • In contrast, omega-agatoxin IVA abolished IPSPs generated by st. lucidum and st. oriens interneurons, but omega-conotoxin MVIIA had no effect [8].
  • In contrast, areas rich in unmyelinated nerve fibers, such as the mossy fibers of the dentate granule cells, the stratum radiatum and stratum oriens of the hippocampus, and the molecular layer of the cerebellum, are strongly immunoreactive for RII but not RI [9].
  • In the CA3 pyramidal cells in hippocampal slices from mutant mice, inhibitory postsynaptic currents evoked by direct electrical stimulation of the interneuron in the striatum oriens were characterized by reduced quantal content compared with those in wild type [10].
  • Dense, AT8-immunopositive deposits were found in the subiculum, stratum oriens of hippocampal field CA1, and the hilus of the dentate gyrus [11].
  • The dendrites of MFA interneurons were mainly located in the strata radiatum and oriens, suggesting that these cells are primarily activated by associational and commissural fibers [12].

Chemical compound and disease context of (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid

  • At 4-7 days after the induced ischemia, immunoreactivities of the CaN A alpha isoform in CA1 pyramidal cells were markedly reduced, whereas they were enhanced in the CA1 radiatum and oriens layers [13].
  • Present results suggest that excitoneurotoxicity mediated through post-synaptic metabotropic glutamate receptor 1alpha may be involved in degeneration and death of interneurons in the hilus of dentate gyrus, and the border between stratum oriens and alveus of CA1 in the early stage after pilocarpine-induced status epilepticus [14].
  • Following anoxia, there is an initial addition increase in stratum oriens of CA1 and CA3 glucose utilization that is followed by a decline in glucose utilization in all slice regions within an hour of the insult [15].

Biological context of (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid


Anatomical context of (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid

  • Protein kinase C redistribution within CA3 stratum oriens during acquisition of nictitating membrane conditioning in the rabbit [21].
  • Somatostatin/GABA-immunoreactive neurons were localized mainly in the stratum oriens and in the hilus of the fascia dentata [22].
  • In contrast, astrocytes appeared to be activated in multiple hippocampal cell layers including stratum radiatum and stratum oriens [23].
  • In all regions examined by electron microscopy (cortex, CPN, and the stratum oriens of CA1), PROT labeling was observed primarily within subpopulations of axon terminals forming asymmetric excitatory-type synapses [24].
  • The GluR-5 gene shows peaks of expression around the period of birth in the sensory cortex (layers II, III, and IV), in CA1 hippocampal interneurons in the stratum oriens, in the septum, and in the thalamus [25].

Associations of (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid with other chemical compounds

  • Based on responses to metabotropic glutamate receptor (mGluR) activation, we have characterized two distinct classes of interneuron in stratum (st.) oriens of the CA1 region of hippocampus [26].
  • Through the use of selective opioid agonists and biocytin-filled whole-cell electrodes, interneurons possessing somata located within stratum oriens of hippocampal slices were classified according to the location of their primary axon termination and the expression of mu- or delta-opioid receptors [27].
  • The actions of mu- and delta-opioid agonists (DAMGO and DPDPE, respectively) on GABAergic interneurons in stratum oriens of area CA1 of the hippocampus were examined by using whole-cell voltage-clamp recordings in brain slices [28].
  • High resolution studies of the GABAA receptor have further suggested that a decrease of disinhibitory GABAergic activity (i.e., GABA-to-GABA) in stratum pyramidale of CA3 may coexist with reduced inhibitory modulation (i.e., GABA-to-excitatory pyramidal neuron) in the stratum oriens of this same sector [29].
  • Fifteen days after NMDA injection, neuronal loss with preservation of architecture was observed in stratum oriens, pyramidale, radiatum, lacunosum-moleculare, and stratum moleculare of Ammon's horn, and in radial and granular layers of the dentate gyrus [30].

Gene context of (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid

  • Monoiodinated peptide YY binding, mainly representing Y2-Rs, was down-regulated by 85% in the CA1 strata oriens and radiatum and by 50-65% in the CA3 stratum oriens 110-140 days postinoculation [31].
  • Additionally, staining was observed in neurons in the stratum oriens, a population of neurons at the periphery of the CA4 sector, scattered, probably short-axon perikarya in the CA1 sector, and fibers in the perforant path and the molecular layer of the dentate gyrus [32].
  • Binding sites for 125I-PYY are most concentrated in the lateral septum, stratum oriens, and radiatum of the hippocampus, amygdala, piriform cortex, entorhinal cortex, several thalamic nuclei, including the reuniens and lateral posterior nuclei, and substantia nigra, pars compacta, and pars lateralis [33].
  • They are numerous in the strata lacunosum-moleculare and radiatum of CA1-CA3, in the hilus, and in the molecular layer of the dentate gyrus, but less common in stratum oriens and alveus, and rare in the principal cell layers [34].
  • The Fmr1 knockout mice exhibited a pattern of Timm granule-staining within the stratum oriens of subfield CA3 and the inner molecular layer that was significantly different than staining seen in wild-type animals [35].

Analytical, diagnostic and therapeutic context of (4aR,6aS,6bR,12aS,14bS)-10-acetoxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylic acid

  • Intracellularly recorded EPSPs resulting from single-volley stimulation at low frequency (0.15-0.1 Hz) in the stratum radiatum or oriens were paired with depolarizing current pulses (50-100 msec) injected through the recording microelectrode [36].
  • By confocal laser microscopy, we show that P2X7 is present at the synaptic level of fibers extending from the CA1-2 pyramidal cell layer throughout the strata oriens and radiatum, but absent on oligodendrocytes, astrocytes or neuronal cell bodies [37].
  • We measured total calcium and potassium contents in the stratum oriens, pyramidale, radiatum, and moleculare of the CA1 and CA3 sectors, using particle induced x-ray emission (PIXE) in the proton microprobe mode [38].
  • Using the isolated juvenile (7-14 days) mouse whole hippocampus preparation, which contains intact complex local circuitry, 145 dual whole cell recordings were made from stratum oriens (s.o.) interneurones under infrared microscopy [39].
  • The membrane metalloenzyme endopeptidase-24.11 has been localized by immunocytochemistry in the porcine hippocampus in the stratum oriens and stratum radiatum [40].


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  13. Isoform-specific redistribution of calcineurin A alpha and A beta in the hippocampal CA1 region of gerbils after transient ischemia. Hashimoto, T., Kawamata, T., Saito, N., Sasaki, M., Nakai, M., Niu, S., Taniguchi, T., Terashima, A., Yasuda, M., Maeda, K., Tanaka, C. J. Neurochem. (1998) [Pubmed]
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  21. Protein kinase C redistribution within CA3 stratum oriens during acquisition of nictitating membrane conditioning in the rabbit. Scharenberg, A.M., Olds, J.L., Schreurs, B.G., Craig, A.M., Alkon, D.L. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  22. Different populations of GABAergic neurons in the visual cortex and hippocampus of cat contain somatostatin- or cholecystokinin-immunoreactive material. Somogyi, P., Hodgson, A.J., Smith, A.D., Nunzi, M.G., Gorio, A., Wu, J.Y. J. Neurosci. (1984) [Pubmed]
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  31. Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease. Diez, M., Koistinaho, J., Dearmond, S.J., Groth, D., Prusiner, S.B., Hökfelt, T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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  37. Synaptic P2X7 and oxygen/glucose deprivation in organotypic hippocampal cultures. Cavaliere, F., Amadio, S., Sancesario, G., Bernardi, G., Volonté, C. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
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  39. Electrotonic coupling between stratum oriens interneurones in the intact in vitro mouse juvenile hippocampus. Zhang, X.L., Zhang, L., Carlen, P.L. J. Physiol. (Lond.) (2004) [Pubmed]
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