Pilocarpine-induced acute seizure causes rapid area-specific astrogliosis and alters purinergic signaling in rat hippocampus.

The progressive nature of acquired epilepsy warrants a thorough examination of acute changes that occur immediately after an epileptogenic insult to better understand the cellular and molecular mechanisms that trigger epileptogenesis. Astrocytes are important regulators of neuronal functions and emerging evidence suggests an involvement of astrocytic purinergic signaling in the etiology of acquired epilepsy. However, how astrocytic purinergic signaling responds immediately after an acute seizure or an epileptogenic insult to impact epileptogenesis is not well studied. In the present study, we report area-specific rapid onset of astrocytic changes in morphology, as well as in expression and functional activity of the purinergic signaling in the hippocampus that occur immediately after pilocarpine-induced stage 5 seizure. After 3 hr of stage 5 acute seizure, hippocampal astrocytes show increased intrinsic calcium activity in stratum radiatum as well as reactive astrogliosis in the stratum lacunosum moleculare and hilus regions of the hippocampus. Hilar astrocytes also upregulated the expression of P2Y1 and P2Y2 metabotropic purinergic receptors. Subsequently, P2Y1 exhibited a functional upregulation by showing a significantly higher intracellular calcium rise in ex-vivo hippocampal slices on P2Y1 activation. Our results suggest that hippocampal astrocytes undergo rapid area-specific morphological and functional changes immediately after the commencement of the seizure activity and purinergic receptors upregulation is one of the earliest changes in response to seizure activity. These changes can be considered acute astrocytic responses to seizure activity which can potentially drive the epileptogenesis and can be explored further to identify astrocyte-specific targets for seizure therapy.

Design of an aluminium ion battery with a graphyne host: lowest volume expansion, high stability and low diffusion barriers.

Commercialization of aluminium ion battery (AIB) requires limited volume expansion of the host cathode materials after AlCl4 intercalation, lower activation barrier, high theoretical specific capacity (TSC), cyclic durability and thermodynamic stability. Most of the carbon and non-carbon based cathode hosts explored so far failed to address the issue of volume expansion and there is a lack of clarity about thermodynamic stability. In this work, we employed multipronged first principles computational approaches on α- and γ-graphyne (GY) and showed that α-GY as a promising cathode host addresses each of the above concerns. Both α and γ-GYs provide ample space to accommodate more number of AlCl4 molecules leading to a high TSC of 186 mA h g-1 and open circuit voltages of 2.18 and 2.22 V, respectively. The absence of bond dissociation of AlCl4 and deformation of GY sheets at 300 and 600 K, as revealed by ab initio molecular dynamics (AIMD) simulation, indicates the stability of α- and γ-GY with adsorbed AlCl4. α-GY after intercalation shows a volume expansion of 186% which is the lowest among the cathode materials studied so far. The negligible expansion energy per unit surface area (∼0.003 eV Å-2) ensures the reversibility and hence cyclic durability of α-GY. Although the γ-GY shows a volume expansion of 249%, it is still promising. The NEB based diffusion study on monolayer and bilayer GY estimates the activation barriers to be (0.26, 0.06 eV) and (0.42, 0.16 eV) for α and γ phases, respectively. These values are either comparable to or lower than those of earlier reported cathode hosts.

Development of short and long-range magnetic order in the double perovskite based frustrated triangular lattice antiferromagnet Ba[Formula: see text]MnTeO[Formula: see text].

Frustrated magnets based on oxide double perovskites offer a viable ground wherein competing magnetic interactions, macroscopic ground state degeneracy and complex interplay between emergent degrees of freedom can lead to correlated quantum phenomena with exotic excitations highly relevant for potential technological applications. By local-probe muon spin relaxation ([Formula: see text]SR) and complementary thermodynamic measurements accompanied by first-principles calculations, we here demonstrate novel electronic structure and magnetic phases of Ba[Formula: see text]MnTeO[Formula: see text], where Mn[Formula: see text] ions with S = 5/2 spins constitute a perfect triangular lattice. Magnetization results evidence the presence of strong antiferromagnetic interactions between Mn[Formula: see text] spins and a phase transition at [Formula: see text] = 20 K. Below [Formula: see text], the specific heat data show antiferromagnetic magnon excitations with a gap of 1.4 K, which is due to magnetic anisotropy. [Formula: see text]SR reveals the presence of static internal fields in the ordered state and short-range spin correlations high above [Formula: see text]. It further unveils critical slowing-down of spin dynamics at [Formula: see text] and the persistence of spin dynamics even in the magnetically ordered state. Theoretical studies infer that Heisenberg interactions govern the inter- and intra-layer spin-frustration in this compound. Our results establish that the combined effect of a weak third-nearest-neighbour ferromagnetic inter-layer interaction (owing to double-exchange) and intra-layer interactions stabilizes a three-dimensional magnetic ordering in this frustrated magnet.

A generic Slater-Koster description of the electronic structure of centrosymmetric halide perovskites.

The halide perovskites have truly emerged as efficient optoelectronic materials and show the promise of exhibiting nontrivial topological phases. Since the bandgap is the deterministic factor for these quantum phases, here, we present a comprehensive electronic structure study using first-principle methods by considering nine inorganic halide perovskites CsBX3 (B = Ge, Sn, Pb; X = Cl, Br, I) in their three structural polymorphs (cubic, tetragonal, and orthorhombic). A series of exchange-correlation (XC) functionals are examined toward accurate estimation of the bandgap. Furthermore, while 13 orbitals are active in constructing the valence and conduction band spectra, here, we establish that a 4 orbital based minimal basis set is sufficient to build the Slater-Koster tight-binding (SK-TB) model, which is capable of reproducing the bulk and surface electronic structures in the vicinity of the Fermi level. Therefore, like the Wannier based TB model, the presented SK-TB model can also be considered an efficient tool to examine the bulk and surface electronic structures of the halide family of compounds. As estimated by comparing the model study and DFT band structure, the dominant electron coupling strengths are found to be nearly independent of XC functionals, which further establishes the utility of the SK-TB model.

Metal-insulator transition in epitaxial Ga-doped ZnO films via controlled thickness.

Understanding and tuning of metal-insulator transition (MIT) in oxide systems is an interesting and active research topics of condensed matter physics. We report thickness dependent MIT in Ga-doped ZnO (Ga:ZnO) thin films grown by pulsed laser deposition technique. From the electrical transport measurements, we find that while the thinnest film (6 nm) exhibits a resistivity of 0.05 Ω cm, lying in the insulating regime, the thickest (51 nm) has resistivity of 6.6 × 10-4 Ω cm which shows metallic type of conduction. Our analysis reveals that the Mott's variable range hopping model governs the insulating behavior in the 6 nm film whereas the 2D weak localization (WL) phenomena is appropriate to explain the electron transport in the thicker Ga:ZnO films. Magnetoresistance study further confirms the presence of strong localization in 6 nm film while WL is observed in 20 nm and above thicker films. From the density functional calculations, it is found that due to surface reconstruction and Ga doping, strong crystalline disorder sets in very thin films to introduce localized states and thereby, restricts the donor electron mobility.

Maximizing Short Circuit Current Density and Open Circuit Voltage in Oxygen Vacancy-Controlled Bi1-xCaxFe1-yTiyO3-δ Thin-Film Solar Cells.

Designing solid-state perovskite oxide solar cells with large short circuit current (JSC) and open circuit voltage (VOC) has been a challenging problem. Epitaxial BiFeO3 (BFO) films are known to exhibit large VOC (>50 V). However, they exhibit low JSC (≪µA/cm2) under 1 Sun illumination. In this work, taking polycrystalline BiFeO3 thin films, we demonstrate that oxygen vacancies (VO) present within the lattice and at grain boundary (GB) can explicitly be controlled to achieve high JSC and VOC simultaneously. While aliovalent substitution (Ca2+ at Bi3+ site) is used to control the lattice VO, Ca and Ti cosubstitution is used to bring out only GB-VO. Fluorine-doped tin oxide (FTO)/Bi1-xCaxFe1-yTiyO3-δ/Au devices are tested for photovoltaic characteristics. Introducing VO increases the photocurrent by four orders (JSC ∼ 3 mA/cm2). On the contrary, VOC is found to be <0.5 V, as against 0.5-3 V observed for the pristine BiFeO3. Ca and Ti cosubstitution facilitate the formation of smaller crystallites, which in turn increase the GB area and thereby the GB-VO. This creates defect bands occupying the bulk band gap, as inferred from the diffused reflection spectra and band structure calculations, leading to a three-order increase in JSC. The cosubstitution, following a charge compensation mechanism, decreases the lattice VO concentration significantly to retain the ferroelectric nature with enhanced polarization. It helps to achieve VOC (3-8 V) much larger than that of BiFeO3 (0.5-3 V). It is noteworthy that as Ca substitution maintains moderate crystallite size, the lattice VO concentration dominates GB-VO concentration. Notwithstanding, both lattice and GB-VO contribute to the increase in JSC; the former weakens ferroelectricity, and as a consequence, undesirably, VOC is lowered well below 0.5 V. Using optimum JSC and VOC, we demonstrate that the efficiency ∼0.22% can be achieved in solid-state BFO solar cells under AM 1.5 one Sun illumination.

Giant photovoltaic response in band engineered ferroelectric perovskite.

Recently the solar energy, an inevitable part of green energy source, has become a mandatory topics in frontier research areas. In this respect, non-centrosymmetric ferroelectric perovskites with open circuit voltage (VOC) higher than the bandgap, gain tremendous importance as next generation photovoltaic materials. Here a non-toxic co-doped Ba1-x(Bi0.5Li0.5) x TiO3 ferroelectric system is designed where the dopants influence the band topology in order to enhance the photovoltaic effect. In particular, at the optimal doping concentration (x opt ~ 0.125) the sample reveals a remarkably high photogenerated field EOC = 320 V/cm (VOC = 16 V), highest ever reported in any bulk polycrystalline non-centrosymmetric systems. The band structure, examined through DFT calculations, suggests that the shift current mechanism is key to explain the large enhancement in photovoltaic effect in this family.

Orbital driven impurity spin effect on the magnetic order of quasi-3D cupric oxide.

Density functional calculations are performed to study the magnetic order of the severely distorted square planar cupric oxide (CuO) and local spin disorder in it in the presence of the transition metal impurities M (=Cr, Mn, Fe, Co and Ni). The distortion in the crystal structure, arisen to reduce the band energy by minimizing the covalent interaction, creates two crisscrossing zigzag spin-1/2 chains. From the spin dimer analysis we find that while the spin chain along [Formula: see text] has strong Heisenberg type antiferromagnetic coupling (J ~ 127 meV), along [Formula: see text] it exhibits weak, but robust, ferromagnetic coupling (J ~ 9 meV) mediated by reminiscent p-d covalent interactions. The impurity effect on the magnetic ordering is independent of M and purely orbital driven. If the given spin-state of M is such that the [Formula: see text] orbital is spin-polarized, then the original long-range ordering is maintained. However, if [Formula: see text] orbital is unoccupied, the absence of corresponding covalent interaction breaks the weak ferromagnetic coupling and a spin-flip takes place at the impurity site leading to breakdown of the long range magnetic ordering.

First principles study of the electronic structure and magnetic properties of spin chain compounds: Ca3ZnMnO6 and Ca3ZnCoO6.

We have studied the electronic structure and magnetism of the spin chain compounds Ca3ZnMnO6 and Ca3ZnCoO6 using density functional theory with generalised gradient approximation (GGA). In agreement with experiment our calculations reveal that high spin (HS) state for Mn(4+) ion and low spin (LS) state for Co(4+) ion stabilize the magnetic structure of the respective compounds. The magnetic exchange paths, calculated using Nth order muffin-tin orbital downfolding method, shows dominant intra-chain exchange interaction between the magnetic ions (Mn, Co) is antiferromagnetic for Ca3ZnMnO6 and ferromagnetic for Ca3ZnCoO6. The magnetic order of both the compounds is in accordance with the Goodenough-Kanamori-Anderson rules and is consistent with the experimental results. Finally we have investigated the importance of spin-orbit coupling (SOC) in these compounds. While SOC practically has no effect for the Mn system, it is strong enough to favor the spin quantization along the chain direction for the Co system in the LS state.

Unconventional Magnetism and Band Gap Formation in LiFePO4: Consequence of Polyanion Induced Non-planarity.

Oxygen plays a critical role in strongly correlated transition metal oxides as crystal field effect is one of the key factors that determine the degree of localization of the valence d/f states. Based on the localization, a set of conventional mechanisms such as Mott-Hubbard, Charge-transfer and Slater were formulated to explain the antiferromagnetic and insulating (AFI) phenomena in many of these correlated systems. From the case study on LiFePO4, through density-functional calculations, we demonstrate that none of these mechanisms are strictly applicable to explain the AFI behavior when the transition metal oxides have polyanions such as (PO4)(3-). The symmetry-lowering of the metal-oxygen complex, to stabilize the polyanion, creates an asymmetric crystal field for d/f states. In LiFePO4 this field creates completely non-degenerate Fe-d states which, with negligible p-d and d-d covalent interactions, become atomically localized to ensure a gap at the Fermi level. Due to large exchange splitting, high spin state is favored and an antiferromagnetic configuration is stabilized. For the prototype LiFePO4, independent electron approximation is good enough to obtain the AFI ground state. Inclusion of additional correlation measures like Hubbard U simply amplifies the gap and therefore LiFePO4 can be preferably called as weakly coupled Mott insulator.

AMPA receptor activation causes preferential mitochondrial Ca²âº load and oxidative stress in motor neurons.

It is well established that motor neurons are highly vulnerable to glutamate induced excitotoxicity. The selective vulnerability of these neurons has been attributed to AMPA receptor mediated excessive rise in cytosolic calcium and consequent mitochondrial Ca(2+) loading. Earlier we have reported that in motor neurons a generic rise in [Ca(2+)]i does not always lead to mitochondrial Ca(2+) loading and membrane depolarization but it occurs upon AMPA receptor activation. The mechanism of such specific mitochondrial involvement upon AMPA receptor activation is not known. The present study examines the mitochondrial Ca(2+) regulation and oxidative stress in spinal cord neurons upon AMPA subtype of glutamate receptor activation. Stimulating the spinal neurons with AMPA exhibited a sharp rise in [Ca(2+)]m in both motor and other spinal neurons that was sustained up to the end of recording time of 30min. The rise in [Ca(2+)]m was substantially higher in motor neurons than in other spinal neurons which could be due to the differential mitochondrial homeostasis in two types of neurons. To examine this possibility, we measured AMPA induced [Ca(2+)]m loading in the presence of mitochondrial inhibitors. In both cell types the AMPA induced [Ca(2+)]m loading was blocked by mitochondrial calcium uniporter blocker ruthenium red. In motor neurons it was also inhibited substantially by CGP37157 and cyclosporine-A, the blockers of Na(+)/Ca(2+) exchanger and mitochondrial permeability transition pore (MPTP) respectively, whereas no effect of these agents was observed in other spinal neurons. Thus in motor neurons the Ca(2+) sequestration by mitochondria occurs through mitochondrial calcium uniporter as well as due to reversal of Na(+)/Ca(2+) exchanger, in contrast the latter pathway does not contribute in other spinal neurons. The ROS formation was inhibited by nitric oxide synthase (NOS) inhibitor L-NAME in both types of neurons, however the mitochondrial complex-I inhibitor rotenone suppressed the ROS formation only in motor neurons. It appears that activation of cytoplasmic nNOS leads to ROS formation in both types of spinal neurons but mitochondria is the major source of ROS in motor neurons. Spinal neurons exhibited a significant time dependent fall in glutathione (GSH) level. The GSH level in motor neurons did not recover even at 24h after AMPA exposure, whereas the other spinal neurons exhibited a tendency to maintain the GSH after a certain level suggesting that the oxidative stress is arrested in other spinal neurons but it continues to increase in motor neurons. Thus our results demonstrate that upon AMPA receptor stimulation the motor neurons employ some additional pathways for regulation of mitochondrial calcium and oxidative stress as compared to other spinal neurons. It is suggested that such differential signaling mechanisms in motor neurons could be crucial for their selective vulnerability to excitotoxicity.

Does toxic defence in Nycticebus spp. relate to ectoparasites? The lethal effects of slow loris venom on arthropods.

The venom produced by slow lorises (Nycticebus spp.) is toxic both intra- and inter-specifically. In this study we assessed the ecoparasite repellent properties of their venom. We tested venom from two Indonesian slow loris species: Nycticebus javanicus and Nycticebus coucang. Arthropods directly exposed to brachial gland secretions mixed with saliva from both species were immediately impaired or exhibited reduced activity (76%), and often died as a result (61%). We found no significant difference in the result of 60-min trials between N. coucang and N. javanicus [X(2)(1, n = 140) = 2.110, p = 0.3482]. We found evidence that the degree of lethality of the venom varies according to the arthropod taxa to which it is exposed. While most maggots (84%) were initially impaired from the venom after 10 min, maggots died after a 1 h trial 42% of the time. In contrast, at the end of 1 h trial, spiders died 78% of the time. For all arthropods, the average time to death from exposure was less than 25 min (M = 24.40, SD = 22.60). Ectoparasites including ticks, members of the arachnid order, are known to transmit pathogens to hosts and may be an intended target of the toxic secretions. Our results suggest that one function of slow loris venom is to repel parasites that affect their fitness, and that their topical anointing behaviour may be an adaptive response to ectoparasites.

Depalmitoylation preferentially downregulates AMPA induced Ca2+ signaling and neurotoxicity in motor neurons.

Excessive activation of AMPA receptor has been implicated in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). However, it is not clear why motor neurons are preferentially sensitive to AMPA receptor mediated excessive [Ca(2+)]i rise and excitotoxicity. In the present study we examined whether palmitoylation regulates Ca(2+) permeability of AMPA receptor and excitotoxicity in cultured spinal cord neurons. We adapted chronic 2-bromopalmitate (2-BrP) treatment to achieve depalmitoylation and examined its effect on the cytotoxicity in spinal cord neurons exposed to AMPA. The change in AMPA induced signaling and cytotoxicity in motor neurons and other spinal neurons under identical conditions of exposure to AMPA was studied. 2-BrP treatment inhibited AMPA induced rise in [Ca(2+)]i and cytotoxicity in both types of neurons but the degree of inhibition was significantly higher in motor neurons as compared to other spinal neurons. The AMPA induced [Na(+)]i rise was moderately affected in both type of neurons on depalmitoylation. Depalmitoylation reduced the expression levels of AMPA receptor subunits (GluR1 and GluR2) and also PSD-95 but stargazin levels remained unaffected. Our results demonstrate that 2-BrP attenuates AMPA receptor activated Ca(2+) signaling and cytotoxicity preferentially in motor neurons and suggest that AMPA receptor modulation by depalmitoylation could play a significant role in preventing motor neuron degeneration.

Role of gentian violet paint in burn wound management: a prospective randomised control trial.

In tribal part of central India burn remains a major cause of morbidity and mortality. Burn management is carried out in conventional manner in most places. The study carried out at Chhatisgarh Institute of Medical Sciences, Bilaspur was Intended to evaluate the efficacy and outcome of 0.5% gentian violet paint local application over conventional dressing treatment of burn wound. The study encompasses 400 patients of burn of varied aetiology admitted in burn ward whose total body surface area of burn was 15% to 50%. The patients receiving conventional treatment were in group I (n=200), and those with gentian violet paint local application formed group II (n= 200). Although, fibrosis of the burn wound, hypertrophic scar were slightly higher in second group it was observed gentian violet paint local application, healed it in 6-8 weeks without severe sepsis and need for skin grafting. From the study it can be concluded that markedly inexpensive gentian violet paint is an useful alternative, for burn wound management.

AMPA induced Ca2+ influx in motor neurons occurs through voltage gated Ca2+ channel and Ca2+ permeable AMPA receptor.

The rise in intracellular Ca(2+) mediated by AMPA subtype of glutamate receptors has been implicated in the pathogenesis of motor neuron disease, but the exact route of Ca(2+) entry into motor neurons is not clearly known. In the present study, we examined the role of voltage gated calcium channels (VGCCs) in AMPA induced Ca(2+) influx and subsequent intracellular signaling events responsible for motor neuron degeneration. AMPA stimulation caused sodium influx in spinal neurons that would depolarize the plasma membrane. The AMPA induced [Ca(2+)](i) rise in motor neurons as well as other spinal neurons was drastically reduced when extracellular sodium was replaced with NMDG, suggesting the involvement of voltage gated calcium channels. AMPA mediated rise in [Ca(2+)](i) was significantly inhibited by L-type VGCC blocker nifedipine, whereas ω-agatoxin-IVA and ω-conotoxin-GVIA, specific blockers of P/Q type and N-type VGCC were not effective. 1-Napthyl-acetyl spermine (NAS), an antagonist of Ca(2+) permeable AMPA receptors partially inhibited the AMPA induced [Ca(2+)](i) rise but selectively in motor neurons. Measurement of AMPA induced currents in whole cell voltage clamp mode suggests that a moderate amount of Ca(2+) influx occurs through Ca(2+) permeable AMPA receptors in a subpopulation of motor neurons. The AMPA induced mitochondrial calcium loading [Ca(2+)](m), mitochondrial depolarization and neurotoxicity were also significantly reduced in presence of nifedipine. Activation of VGCCs by depolarizing concentration of KCl (30mM) in extracellular medium increased the [Ca(2+)](i) but no change was observed in mitochondrial Ca(2+) and membrane potential. Our results demonstrate that a subpopulation of motor neurons express Ca(2+) permeable AMPA receptors, however the larger part of Ca(2+) influx occurs through L-type VGCCs subsequent to AMPA receptor activation and consequent mitochondrial dysfunction is the trigger for motor neuron degeneration. Nifedipine is an effective protective agent against AMPA induced mitochondrial stress and degeneration of motor neurons.

Thrombin like activity of Asclepias curassavica L. latex: action of cysteine proteases.

AIM OF THE STUDY: To validate the scientific basis of plant latex to stop bleeding on fresh cuts. Cysteine protease(s) from Asclepias curassavica (Asclepiadaceae) plant latex was assessed for pro-coagulant and thrombin like activities. MATERIALS AND METHODS: A waxy material from the latex of Asclepias curassavica latex was removed by freezing and thawing. The resulted latex enzyme fraction was assayed for proteolytic activity using denatured casein as substrate. Its coagulant activity and thrombin like activity were determined using citrated plasma and pure fibrinogen, respectively. Inhibition studies were performed using specific protease inhibitors to know the type of protease. RESULTS: The latex enzyme fraction exhibited strong proteolytic activity when compared to trypsin and exerted pro-coagulant action by reducing plasma clotting time from 195 to 58 s whereas trypsin reduced clotting time marginally from 195 to 155 s. The pro-coagulant activity of this enzyme fraction was exerted by selectively hydrolyzing A alpha and B beta subunits of fibrinogen to form fibrin clot when pure fibrinogen was used as substrate as assessed by fibrinogen-agarose plate method and fibrinogen polymerization assay. Trypsin failed to induce any fibrin clot under similar conditions. The electrophoretic pattern of latex enzyme fraction-induced fibrin clot was very much similar to that of thrombin-induced fibrin clot and mimic thrombin like action. The proteolytic activity including thrombin like activity of Asclepias curassavica latex enzyme fraction was completely inhibited by iodoaceticacid (IAA). CONCLUSION: Cysteine proteases from Asclepias curassavica latex exhibited strong pro-coagulant action and were found to be specific in its action (Thrombin like). This could be the basis for the use of plant latex in pharmacological applications that justify their use as folk medicine.

Chlorin p6 preferentially localizes in endoplasmic reticulum and Golgi apparatus and inhibits Ca(2+) release from intracellular store.

Subcellular localization of chlorin p6 in human cerebral glioma (U-87MG) cells was studied using laser scanning confocal microscopy. Localization in sub cellular organelles was ascertained by double labeling with specific fluorescent markers of subcellular organelles. The results reveal that chlorin p6 binds to multiple cellular sites but preferential binding sites are endoplasmic reticulum and Golgi apparatus and it does not bind to mitochondria. Significantly the drug localization pattern of proliferating and differentiated cells was notably distinct. In proliferating cells the internalization of drug was faster than in differentiated cells. Localization of chlorin p6 into the cells inhibited Ca(2+) release from endoplasmic reticulum and deregulated cellular Ca(2+) signalling. These results suggest that the fluorescence imaging pattern of chlorin p6 could be useful in identifying the proliferating and differentiated population of cells in tumor tissue.

Spin-polarized two-dimensional electron gas at oxide interfaces.

The possibility of formation of a fully spin-polarized 2D electron gas at the SrMnO_3/(LaMnO_3)_1/SrMnO_3 heterostructure is predicted from density-functional calculations. The La(d) electrons become confined in the direction normal to the interface in the electrostatic potential well of the positively charged layer of La atoms, acting as electron donors. These electrons mediate a ferromagnetic alignment of the Mn t_2g spins near the interface via Zener double exchange and become, in turn, spin-polarized due to the internal magnetic fields of the Mn moments.

Nitric oxide-mediated modulation of synaptic activity by astrocytic P2Y receptors.

We investigated the mechanism of synaptic suppression by P2Y receptors in mixed hippocampal cultures wherein networked neurons exhibit synchronized Ca(2+) oscillations (SCO) due to spontaneous glutamatergic synaptic transmission. Pharmacological studies suggested that SCO suppression was mediated by P2Y2/P2Y4 receptors. Immunostaining studies and characterization of ATP/UTP-stimulated Ca(2+) responses in solitary neurons and astrocytes revealed that the SCO attenuation was effectuated by astrocytes. We demonstrate that nitric oxide released from activated astrocytes causes synaptic suppression by inhibiting neurotransmitter release. Physiological concentrations of ATP and UTP evoked NO production in astrocytes. SCO suppression was considerably diminished by removal of extracellular NO by membrane-impermeable scavenger c-PTIO or by pretreatment of cells with nitric oxide synthase inhibitor L-NAME. The nitric oxide donor DETA/NO effectively suppressed the SCO. ATP/UTP inhibited KCl-induced exocytosis at presynaptic terminals in an NO-dependent manner. In the absence of exogenously added ATP/UTP, both the NO scavenger and NOS inhibitor enhanced the frequency of SCO, implying that astrocytes release NO during spontaneous synaptic activity and exert a suppressive effect. We report for the first time that under physiological conditions astrocytes use NO as a messenger molecule to modulate the synaptic strength in the networked neurons.

NMDA and non-NMDA receptor-mediated differential Ca2+ load and greater vulnerability of motor neurons in spinal cord cultures.

Glutamate receptor activated neuronal cell death has been implicated in the pathogenesis of motor neuron disease but the molecular mechanism responsible for neuronal dysfunction needs to be elucidated. In the present study, we examined the contribution of NMDA and non-NMDA sub-types of glutamate receptors in selective vulnerability of motor neurons. Glutamate receptor activated Ca2+ signaling, mitochondrial functions and neurotoxicity in motor neurons and other spinal neurons were studied in mixed spinal cord primary cultures. Exposure of cells to glutamate receptor agonists glutamate, NMDA and AMPA elevated the intracellular Ca2+, mitochondrial Ca2+ and caused mitochondrial depolarization and cytotoxicity in both motor neurons and other spinal neurons but a striking difference was observed in the magnitude and temporal patterns of the [Ca2+]i responses between the two neuronal cell types. The motor neurons elicited higher Ca2+ load than the other spinal neurons and the [Ca2+]i levels were elevated for a longer duration in motor neurons. AMPA receptor stimulation was more effective than NMDA. Both the NMDA and non-NMDA receptor antagonists APV and NBQX inhibited the Ca2+ entry and decreased the cell death significantly; however, NBQX was more potent than APV. Our results demonstrate that both NMDA and non-NMDA sub-types of glutamate receptors contribute to glutamate-mediated motor neuron damage but AMPA receptors play the major role. AMPA receptor-mediated excessive Ca2+ load and differential handling/regulation of Ca2+ buffering by mitochondria in motor neurons could be central in their selective vulnerability to excitotoxicity.