bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulfur(lone-pair)…π interactions with FAD in flavoenzymes
Authors: Silva Rui F.N. , Sacco Antônio César S. , Caracelli Ignez , Zukerman-Schpector Julio , Tiekink Edward R.T. 
Published: April 2018

AbstractThe interactions of π-systems with lone-pairs of electrons are known and have been described in biological systems, involving lone-pairs derived from metals, metalloids, sulfur, oxygen and nitrogen. This study describes a bibliographic survey of the disulfide-bound sulfur(lone-pair) interactions with π-systems residing in the flavin adenine dinucleotide (FAD) cofactor of oxidoreductase enzymes (flavoenzymes). Thus, of the 172 oxidoreductase enzymes evaluated for gamma-S(lone-pair)…π(FAD) interactions, 96 proteins (56%) exhibited these interactions corresponding; 61% of 350 the constituent monomers featured at least one gamma-S(lone-pair)…π(FAD) interaction. Two main points of association between the S(lone-pair) and the isoalloxazine moiety of FAD were identified, namely at the centroid of the bond linking the uracil and pyrazine rings (60%), and the centroid of the uracil ring (37%). Reflecting the nature of the secondary structure in three prominent classes of oxidoreductase enzymes: glutathione disulfide reductases (GR; 21 proteins), trypanothione disulfide reductases (TR, 14) and sulfhydryl oxidases (SOX, 22), the approach of the gamma-S(lone-pair) to the FAD residue was to the si-face of the isoalloxazine ring system, i.e. to the opposite side as the carbonyl residue, for all GR and TR examples, and to the re-face for all SOX examples. Finally, the attractive nature of the gamma-S(lone-pair)…π(FAD) interactions was confirmed qualitatively by an examination of the non-covalent interaction plots.
Multiple Components of Ca2+Channel Facilitation in Cerebellar Granule Cells: Expression of Facilitation during Development in Culture
Authors: Parri H. Rheinallt , Lansman Jeffry B. 
Published: April 2018

The contribution of pharmacologically distinct Ca2+channels to prepulse-induced facilitation was studied in mouse cerebellar granule cells. Ca2+channel facilitation was measured as the percentage increase in the whole-cell current recorded during a test pulse before and after it was paired with a positive prepulse. The amount of facilitation was small in recordings made during the first few days in tissue culture but increased substantially after 1 week. L-type channels accounted for the largest proportion of facilitation in 1-week-old cells (60–70%), whereas N-type channels contributed very little (∼3%). The toxins ω-agatoxin IVa or ω-conotoxin MVIIC (after block of N-, L-, and P-type channels) each blocked a small percentage of facilitation (∼12 and 14%, respectively). Perfusion of cells with GTP-γ-S enhanced the facilitation of N-type channels, whereas it inhibited facilitation of L-type channels. During developmentin vitro, the contribution of L-type channels to the whole-cell current decreased. Single-channel recordings showed the presence of 10 and 15 pS L-type Ca2+channels in 1-d-old cells. After 1 week in culture, a ∼25 pS L-type channel dominated recordings from cell-attached patches. Positive prepulses increased the activity of the 25 pS channel but not of the smaller conductance channels. The expression of Ca2+channel facilitation during development may contribute to changes in excitability that allow frequency-dependent Ca2+influx during the period of active synaptogenesis.
Multiple Actions of 1S,3R-ACPD in Modulating Endogenous Synaptic Transmission to Spinal Respiratory Motoneurons
Authors: Dong Xiao-Wei , Morin Didier , Feldman Jack L. 
Published: April 2018

To determine physiological roles of metabotropic glutamate receptors (mGluRs) affecting breathing, we examined the effects of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) on synaptic transmission and excitability of phrenic motoneurons (PMNs) in anin vitroneonatal rat brainstem/spinal cord preparation. The effects of 1S,3R-ACPD were multiple, including reduction of inspiratory-modulated synaptic currents and increase of neuronal excitability via an inward current (Iacpd) associated with a decrease of membrane conductance. The mechanism underlying synaptic depression was examined. We found that 1S,3R-ACPD reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents. The current induced by exogenous AMPA was not significantly affected by 1S,3R-ACPD. These results suggest that 1S,3R-ACPD-induced reduction of inspiratory synaptic currents is mediated by presynaptic mGluRs. We also examined the ionic basis forIacpd. We found thatIacpdhad a reversal potential of approximately −100 mV, close to the estimatedEK+(−95 mV). Elevating extracellular [K+] to 9 mmreduced theIacpdreversal potential to −75 mV. The K+channel blocker Ba2+induced an inward current with a reversal potential at −93 mV associated with a decrease of membrane conductance, closely resembling the effect of 1S,3R-ACPD. Moreover, Ba2+occluded 1S,3R-ACPD effects. In the presence of Ba2+,Iacpdand the 1S,3R-ACPD-induced decrease of membrane conductance were diminished. Our data indicate that the dominant component ofIacpdresults from the blockade of a Ba2+-sensitive resting K+conductance. We conclude that the activation of mGluRs affects the inspiratory-modulated activity of PMNs via distinct mechanisms at pre- and postsynaptic sites.
Hippocampal AstrocytesIn SituRespond to Glutamate Released from Synaptic Terminals
Authors: Porter James T. , McCarthy Ken D. 
Published: April 2018

A long-standing question in neurobiology is whether astrocytes respond to the neuronal release of neurotransmittersin vivo. To address this question, acutely isolated hippocampal slices were loaded with the calcium-sensitive dye Calcium Green-1 and the responses of the astrocytes to electrical stimulation of the Schaffer collaterals were monitored by confocal microscopy. To confirm that the responsive cells were astrocytes, the slices were immunostained for the astrocytic marker glial fibrillary acidic protein. Stimulation of the Schaffer collaterals (50 Hz, 2 sec) resulted in increases in the concentration of intracellular calcium ([Ca2+]i) in the astrocytes located in the stratum radiatum of CA1. The astrocytic responses were blocked by the sodium channel blocker tetrodotoxin, the voltage-dependent calcium channel blocker ω-conotoxin-MVIIC, and the selective metabotropic glutamate receptor antagonist α-methyl-4-carboxyphenylglycine (MCPG). These results suggest that the astrocytic responses were induced by stimulation of metabotropic glutamate receptors on the astrocytes by neuronally released glutamate. The astrocytic responses to neuronal stimulation were enhanced in the presence of the K+channel antagonist 4-aminopyridine (4-AP). Inhibition of the astrocytic responses in the presence of 4-AP required the presence of both MCPG and the ionotropic glutamate receptor antagonist kynurenic acid. These results suggest that higher levels of neuronal activity result in stimulation of both metabotropic and ionotropic glutamate receptors on the astrocytes. Overall, the results indicate that hippocampal astrocytesin situare able to respond to the neuronal release of the neurotransmitter glutamate with increases in [Ca2+]i.
Oligodendroglia Regulate the Regional Expansion of Axon Caliber and Local Accumulation of Neurofilaments during Development Independently of Myelin Formation
Authors: Sánchez Ivelisse , Hassinger Linda , Paskevich Peter A. , Shine H. David , Nixon Ralph A. 
Published: April 2018

Axon caliber may be influenced by intrinsic neuronal factors and extrinsic factors related to myelination. To understand these extrinsic influences, we studied how axon-caliber expansion is related to changes in neurofilament and microtubule organization as axons of retinal ganglion cells interact with oligodendroglia and become myelinated during normal mouse brain development. Caliber expanded and neurofilaments accumulated only along regions of the axon invested with oligodendroglia. Very proximal portions of axons within a region of the optic nerve from which oligodendrocytes are excluded remained unchanged. More distally, these axons rapidly expanded an average of fourfold as soon as they were recruited to become myelinated between postnatal days 9 and 120. Unmyelinated axons remained unchanged. Axons ensheathed by oligodendroglial processes, but not yet myelinated, were intermediate in caliber and neurofilament number. That oligodendrocytes can trigger regional caliber expansion in the absence of myelin was confirmed using three strains of mice with different mutations that prevent myelin formation but allow wrapping of some axons by oligodendroglial processes. Unmyelinated axons persistently wrapped by oligodendrocytes showed full axon caliber expansion, neurofilament accumulation, and appropriately increased lateral spacing between neurofilaments. Thus, signals from oligodendrocytes, independent of myelin formation, are sufficient to induce full axon radial growth primarily by triggering local accumulation and reorganization of the neurofilament network.
Implants of Encapsulated Human CNTF-Producing Fibroblasts Prevent Behavioral Deficits and Striatal Degeneration in a Rodent Model of Huntington’s Disease
Authors: Emerich Dwaine F. , Lindner Mark D. , Winn Shelley R. , Chen Er-Yun , Frydel Beata R. , Kordower Jeffrey H. 
Published: April 2018

Delivery of neurotrophic molecules to the CNS has gained considerable attention as a potential treatment strategy for neurological disorders. In the present study, a DHFR-based expression vector containing the human ciliary neurotrophic factor (hCNTF) was transfected into a baby hamster kidney fibroblast cell line (BHK). Using a polymeric device, encapsulated BHK-control cells and those secreting hCNTF (BHK-hCNTF) were transplanted unilaterally into the rat lateral ventricle. Twelve days later, the same animals received unilateral injections of quinolinic acid (QA; 225 nmol) into the ipsilateral striatum. After surgery, animals were behaviorally tested for apomorphine-induced rotation behavior and for skilled forelimb function using the staircase test. Rats receiving BHK-hCNTF cells rotated significantly less than animals receiving BHK-control cells. No behavioral effects of hCNTF were observed on the staircase test. Nissl-stained sections demonstrated that BHK-hCNTF cells significantly reduced the extent of striatal damage produced by QA. Quantitative analysis of striatal neurons further demonstrated that both choline acetyltransferase- and GAD-immunoreactive neurons were protected by BHK-hCNTF implants. In contrast, a similar loss of NADPH-diaphorase-positive cells was observed in the striatum of both implant groups. Analysis of retrieved capsules revealed numerous viable and mitotically active BHK cells that continued to secrete hCNTF. These results support the concepts that implants of polymer-encapsulated hCNTF-releasing cells can be used to protect striatal neurons from excitotoxic damage and that this strategy may ultimately prove relevant for the treatment of Huntington’s disease.
Synchronous Activity in Locus Coeruleus Results from Dendritic Interactions in Pericoerulear Regions
Authors: Ishimatsu Masaru , Williams John T. 
Published: April 2018

Locus coeruleus (LC) neurons in brain slices from adult rats were studied using intracellular and extracellular recordings to investigate synchronous activity. Spontaneous field potentials were recorded with extracellular electrodes in solutions containing tetraethylammonium chloride (10 mm) and BaCl2(1 mm). These field potentials were found throughout but not outside the LC cell body region. No field potentials were observed in control solutions. Paired recordings showed that field potentials were synchronous in all areas of the LC. The synchronous activity was resistant to tetrodotoxin (1 μm) and to the neurotransmitter receptor blockersd-2-amino-5-phosphonopentanoic acid, bicuculline, 6-cyano-7-nitroquinoxaline-2,3-dione, idazoxan, and strychnine, suggesting that this activity was not synaptically driven. Field potentials were also synchronous with oscillations in membrane potential recorded with intracellular electrodes. The oscillations in membrane potential were 5–30 mV in amplitude and had a biphasic waveform. Neither the frequency nor the waveform of the oscillations was dependent on the membrane potential. The glycyrrhetinic acid derivative carbenoxolone and intracellular acidification with CO2disrupted synchronous activity, suggesting a role of electrotonic coupling. When the cell body region of the LC was isolated from the pericoerulear dendritic regions by sectioning the slice rostral and caudal to the cell body region, synchronous activity was reduced or abolished. Dendritic interaction in the pericoerulear region was also indicated by improved voltage control of the opioid-induced potassium current, as indicated by a shift in the reversal potential to the potassium equilibrium potential. The results suggest that electrical interactions between dendrites outside the cell body region can account for synchronous activity within the nucleus.
Differential Sensitivity of Human Visual Cortex to Faces, Letterstrings, and Textures: A Functional Magnetic Resonance Imaging Study
Authors: Puce Aina , Allison Truett , Asgari Maryam , Gore John C. , McCarthy Gregory 
Published: April 2018

Twelve normal subjects viewed alternating sequences of unfamiliar faces, unpronounceable nonword letterstrings, and textures while echoplanar functional magnetic resonance images were acquired in seven slices extending from the posterior margin of the splenium to near the occipital pole. These stimuli were chosen to elicit initial category-specific processing in extrastriate cortex while minimizing semantic processing. Overall, faces evoked more activation than did letterstrings. Comparing hemispheres, faces evoked greater activation in the right than the left hemisphere, whereas letterstrings evoked greater activation in the left than the right hemisphere. Faces primarily activated the fusiform gyrus bilaterally, and also activated the right occipitotemporal and inferior occipital sulci and a region of lateral cortex centered in the middle temporal gyrus. Letterstrings primarily activated the left occipitotemporal and inferior occipital sulci. Textures primarily activated portions of the collateral sulcus. In the left hemisphere, 9 of the 12 subjects showed a characteristic pattern in which faces activated a discrete region of the lateral fusiform gyrus, whereas letterstrings activated a nearby region of cortex within the occipitotemporal and inferior occipital sulci. These results suggest that different regions of ventral extrastriate cortex are specialized for processing the perceptual features of faces and letterstrings, and that these regions are intermediate between earlier processing in striate and peristriate cortex, and later lexical, semantic, and associative processing in downstream cortical regions.
Dendritic and Postsynaptic Protein Synthetic Machinery
Authors: Gardiol Alejandra , Racca Claudia , Triller Antoine 
Published: April 2018

There is a growing body of evidence that local protein synthesis beneath synapses may provide a novel mechanism underlying plastic phenomena.In vivoandin vitrobiochemical data show that dendrites can perform translation and glycosylation. Using antibodies directed against the eukaryotic protein synthetic machinery, we sought to identify the structures implicated in nonperinuclear translation, namely dendritic and postsynaptic protein synthesis. We performed a morphological and immunocytochemical analysis of ventromedial horn rat spinal cord neurons using both light and electron microscopy.We show at the cellular level that,in vivo, protein synthesis macrocomplexes (ribosomes and eIF-2) as well as the endomembranous system implicated in cotranslational and posttranslational modifications (endoplasmic reticulum and Golgi cisternae) penetrated some dendrites. Membrane-limited organelles of different shape and size are present close to the postsynaptic differentiations of most synapses, independently of their localization on the neuronal surface. We demonstrate (1) that some cisternae are immunoreactive for antibodies against ribosomal proteins and eIF-2, and (2) that markers of endoplasmic reticulum (BiP), intermediate compartment, and Golgi complex (rab1, CTR433, TGN38) label subsets of these subsynaptic organelles.Therefore, these findings indicate that synapses are equipped with the essential elements required for the synthesis and insertion of a well folded and glycosylated transmembrane protein.
GABAergic Neurons that Contain Neuropeptide Y Selectively Target Cells with the Neurokinin 1 Receptor in Laminae III and IV of the Rat Spinal Cord
Authors: Polgár Erika , Shehab Safa A. S. , Watt Christine , Todd Andrew J. 
Published: April 2018

Neuropeptide Y (NPY) is contained in a population of GABAergic interneurons in the spinal dorsal horn and, when administered intrathecally, can produce analgesia. We previously identified a strong monosynaptic link between substance P-containing primary afferents and cells in lamina III or IV with the neurokinin 1 (NK1) receptor. Because some of these cells belong to the spinothalamic tract, they are likely to have an important role in pain mechanisms.In this study, we used confocal microscopy to examine the input to lamina III/IV NK1 receptor-immunoreactive neurons from NPY-containing axons. All of the cells studied received a dense innervation from NPY-immunoreactive axons, and electron microscopy revealed that synapses were often present at points of contact. Most NPY-immunoreactive boutons were also GABAergic, which supports the suggestion that they are derived from local neurons. The association between NPY-containing axons and NK1 receptor-immunoreactive neurons was specific, because postsynaptic dorsal column neurons (which were located in laminae III–V but did not possess NK1 receptors) and lamina I neurons with the NK1 receptor received significantly fewer contacts from NPY-immunoreactive axons. In addition, the NK1 receptor-immunoreactive lamina III/IV cells received few contacts from nitric oxide synthase-containing axons (which belong to a different population of GABAergic dorsal horn neurons). The NPY-containing axons appeared to be targeted to the NK1 receptor-immunoreactive neurons themselves rather than to their associated substance P-immunoreactive inputs.The dense innervation of these cells by NPY-containing axons suggests that they may possess receptors for NPY and that activation of these receptors may contribute to NPY-mediated analgesia.
Sensory Impairments and Delayed Regeneration of Sensory Axons in Interleukin-6-Deficient Mice
Authors: Zhong Jian , Dietzel Irmgard D. , Wahle Petra , Kopf Manfred , Heumann Rolf 
Published: April 2018

Interleukin-6 (IL-6) is a multifunctional cytokine mediating inflammatory or immune reactions. Here we investigated the possible role of IL-6 in the intact or lesioned peripheral nervous system using adult IL-6 gene knockout (IL-6−/−) mice. Various sensory functions were tested by applying electrophysiological, morphological, biochemical, and behavioral methods. There was a 60% reduction of the compound action potential of the sensory branch of IL-6−/−mice as compared with the motor branch in the intact sciatic nerve. Cross sections of L5 DRG of IL-6−/−mice showed a shift in the relative size distribution of the neurons. The temperature sensitivity of IL-6−/−mice was also significantly reduced.After crush lesion of the sciatic nerve, its functional recovery was delayed in IL-6−/−mice as analyzed from a behavioral footprint assay. Measurements of compound action potentials 20 d after crush lesion showed that there was a very low level of recovery of the sensory but not of the motor branch of IL-6−/−mice. Similar results of sensory impairments were obtained with mice showing slow Wallerian degeneration (Wlds) and a delayed lesion-induced recruitment of macrophages. However, in contrast to WldSmice, in IL-6−/−mice we observed the characteristic lesion-induced invasion of macrophages and the upregulation of low-affinity neurotrophin receptor p75 (p75LNTR) mRNA levels identical to those of IL-6+/+mice. Thus, the mechanisms leading to the common sensory deficiencies were different between IL-6−/−and WldSmice. Altogether, the results suggest that interleukin-6 is essential to modulate sensory functionsin vivo.
Supporting Cells Contribute to Control of Hearing Sensitivity
Authors: Flock Åke , Flock Britta , Fridberger Anders , Scarfone Eric , Ulfendahl Mats 
Published: April 2018

The mammalian hearing organ, the organ of Corti, was studied in anin vitropreparation of the guinea pig temporal bone. Asin vivo, the hearing organ responded with an electrical potential, the cochlear microphonic potential, when stimulated with a test tone. After exposure to intense sound, the response to the test tone was reduced. The electrical response either recovered within 10–20 min or remained permanently reduced, thus corresponding to a temporary or sustained loss of sensitivity.Using laser scanning confocal microscopy, stimulus-induced changes of the cellular structure of the hearing organ were simultaneously studied. The cells in the organ were labeled with two fluorescent probes, a membrane dye and a cytoplasm dye, showing enzymatic activity in living cells. Confocal microscopy images were collected and compared before and after intense sound exposure. The results were as follows. (1) The organ of Corti could be divided into two different structural entities in terms of their susceptibility to damage: an inner, structurally stable region comprised of the inner hair cell with its supporting cells and the inner and outer pillar cells; and an outer region that exhibited dynamic structural changes and consisted of the outer hair cells and the third Deiters’ cell with its attached Hensen’s cells. (2) Exposure to intense sound caused the Deiters’ cells and Hensen’s cells to move in toward the center of the cochlear turn. (3) This event coincided with a reduced sensitivity to the test tone (i.e., reduced cochlear microphonic potential). (4) The displacement and sensitivity loss could be reversible. It is concluded that these observations have relevance for understanding the mechanisms behind hearing loss after noise exposure and that the supporting cells take an active part in protection against trauma during high-intensity sound exposure.