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Capacity region and minimum energy function for a variety of delay-tolerant mobile unicast ad hoc networks are studied by using a cell-partitioned model. First, theorems about analytical expressions of network capacity and upper bound of minimum energy function are proposed and proved. Algorithm aiming at maximizing capacity and minimizing energy cost is presented and analyzed by Lyapunov drift method. Second, these two theorems are applied to several types of ad hoc networks. Expressions of network capacity and minimum energy function are obtained. Third, capacity property of a type of hybrid ad hoc networks is analyzed in detail. Relationship among limitation of capacity, node density, and coverage of base stations are investigated. Numerical analysis and simulation are carried out. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The dysfunction of TAR DNA-binding protein-43 (TDP-43) is implicated in neurodegenerative diseases. However, the function of TDP- 43 is not fully elucidated. Here we show that the protein level of endogenous TDP-43 in the nucleus is increased in mouse cortical neurons in the early stages, but return to basal level in the later stages after glutamate accumulation-induced injury. The elevation of TDP-43 results from a downregulation of phosphatase and tensin homolog (PTEN). We further demonstrate that activation of NR2Acontaining NMDA receptors (NR2ARs) leads to PTEN downregulation and subsequent reduction of PTEN import from the cytoplasm to the nucleus after glutamate accumulation. The decrease of PTEN in the nucleus contributes to its reduced association with TDP-43, and thereby mediates the elevation of nuclear TDP-43. We provide evidence that the elevation of nuclear TDP-43, mediated by NR2AR activation and PTEN downregulation, confers protection against cortical neuronal death in the late stages after glutamate accumulation. Thus, this study reveals a NR2AR-PTEN-TDP-43 signaling pathway by which nuclear TDP-43 promotes neuronal survival. These results suggest that upregulation of nuclear TDP-43 represents a self-protection mechanism to delay neurodegeneration in the early stages after glutamate accumulation and that prolonging the upregulation process of nuclear TDP-43 might have therapeutic significance. [ABSTRACT FROM AUTHOR]

Dysfunction of PTEN-induced kinase 1 (PINK1) or DJ-1 promotes neuronal death and is implicated in the pathogenesis of Parkinson’s disease, but the underlying mechanisms remain unclear. Given the roles of N-methyl-d-aspartate receptor (NMDAr)-mediated neurotoxicity in various brain disorders including cerebral ischemia and neurodegenerative diseases, we investigated the effects of PINK1 and DJ-1 on NMDAr function. Using protein overexpression and knockdown approaches, we showed that PINK1 increased NMDAr-mediated whole-cell currents by enhancing the function of NR2A-containing NMDAr subtype (NR2ACNR). However, DJ-1 decreased NMDAr-mediated currents, which was mediated through the inhibition of both NR2ACNR and NR2B-containing NMDAr subtype (NR2BCNR). We revealed that the knockdown of DJ-1 enhanced PTEN expression, which not only potentiated NR2BCNR function but also increased PINK1 expression that led to NR2ACNR potentiation. These results indicate that NMDAr function is differentially regulated by DJ-1-dependent signal pathways DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR. Our results further showed that the suppression of DJ-1, while promoted NMDA-induced neuronal death through the overactivation of PTEN/NR2BCNR-dependent cell death pathway, induced a neuroprotective effect to counteract DJ-1 dysfunction-mediated neuronal death signaling through activating PTEN/PINK1/NR2ACNR cell survival–promoting pathway. Thus, PINK1 acts with DJ-1 in a common pathway to regulate NMDAr-mediated neuronal death. This study suggests that the DJ-1/PTEN/NR2BCNR and DJ-1/PTEN/PINK1/NR2ACNR pathways may represent potential therapeutic targets for the development of neuroprotection strategy in the treatment of brain injuries and neurodegenerative diseases such as Parkinson’s disease. [ABSTRACT FROM AUTHOR]

Dysfunction of PTEN-induced kinase-1 (PINK1) is implicated in neurodegeneration. We report here that oxygen-glucose deprivation (OGD), an in vitro insult mimicking ischemic neuron injury, resulted in a significant reduction of PINK1 protein expression in cultured cortical neurons. The decrease of PINK1 expression was blocked by the antagonists of NMDA receptors. We revealed that the overactivation of NR2B-containing NMDA receptors (NR2BRs) was responsible for the OGD-induced PINK1 reduction. The overactivated NR2BRs also inhibited the phosphorylation, but not the protein expression, of the cell survival-promoting kinase Akt after OGD insult, indicating that OGD-induced reduction of PINK1 protein is specific in the injury paradigm. We further showed that enhancing the protein expression of PINK1 antagonized OGD-induced reduction of Akt phosphorylation, suggesting that Akt may be a downstream target of PINK1 in ischemic neuron injury. Importantly, we provided evidence that both NR2BR antagonist and PINK1 over-expression protected against OGD-induced neuronal death. These results suggest that the overactivation of NR2BRs may contribute to ischemic neuron death through suppressing PINK1-dependent survival signaling. Thus, selectively antagonizing NR2BR signal pathway-induced neurotoxicity may be a potential neuroprotection strategy. [ABSTRACT FROM AUTHOR]

Regulated AMPA receptor (AMPAR) trafficking at excitatory synapses is a mechanism critical to activity-dependent alterations in synaptic efficacy. The role of regulated AMPAR trafficking in insult-induced synaptic remodeling and/or cell death is, however, as yet unclear. Here we show that brief oxygen--glucose deprivation (OGD), an in vitro model of brain ischemia, promotes redistribution of AMPARs at synapses of hippocampal neurons, leading to a switch in AMPAR subunit composition. Ischemic insults promote internalization of glutamate receptor subunit 2 (GluR2)-containing AMPARs from synaptic sites via clathrin-dependent endocytosis and facilitate delivery of GluR2-lacking AMPARs to synaptic sites via soluble N-ethylmaleimide-sensitive factor attachment protein receptordependent exocytosis, evident at early times after insult. The OGD-induced switch in receptor subunit composition requires PKC activation, dissociation of GluR2 from AMPA receptor-binding protein, and association with protein interacting with C kinase-1. We further show that AMPARs at synapses of insulted neurons exhibit functional properties of GluR2-lacking AMPARs. AMPAR-mediated miniature EPSCs exhibit increased amplitudes and enhanced sensitivity to subunit-specific blockers of GluR2-lacking AMPARs, evident at 24 h after ischemia. The OGD-induced alterations in synapticAMPAcurrents require clathrin-mediated receptor endocytosis and PKC activation. Thus, ischemic insults promote targeting of GluR2-lacking AMPARs to synapses of hippocampal neurons, mechanisms that may be relevant to ischemia-induced synaptic remodeling and/or neuronal death. [ABSTRACT FROM AUTHOR]

The widespread distribution of the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) in the adult brain suggests its role in a broad range of brain functions. Here we show evidence supporting a physical interaction of PTEN with a region in the third intracellular loop (3L4F) of the serotonin 5-HT2C receptor (5-HT2cR, formerly 5-HT1c receptor) in cell cultures. PTEN limits agonist-induced phosphorylation of 5-HT2cR through its protein phosphatase activity. We showed the probable existence of PTEN:5-HT2cR complexes in putative dopaminergic neurons in the rat ventral tegmental area (VTA), a brain region in which virtually all abused drugs exert rewarding effects by activating its dopamine neurons. We synthesized the interfering peptide Tat-3L4F, which is able to disrupt PTEN coupling with 5-HT2cR. Systemic application of Tat-3L4F or the 5-HT2cR agonist Ro600175 suppressed the increased firing rate of VTA dopaminergic neurons induced by Δ9-tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana. Using behavioral tests, we found that Tat-3L4F or Ro600175 blocks conditioned place preference of THC or nicotine, and that Ro600175, but not Tat-3L4F, produces anxiogenic effects, penile erection, hypophagia and motor functional suppression. These results suggest a potential strategy for treating drug addiction with the Tat-3L4F peptide. [ABSTRACT FROM AUTHOR]

The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a lipid and protein phosphatase. We report here that PTEN physically associates with the NR1 and NR2B subunits of NMDA receptors (NMDARs) in rat hippocampus. Downregulating the protein expression of PTEN inhibits the function of extrasynaptic NMDARs and decreases NMDAR surface expression, suggesting a crucial role for endogenous PTEN in the modulation of NMDAR-mediated neuronal function. Reducing PTEN expression also enhances Akt/Bad phosphorylation in hippocampal neurons. Importantly, suppressing lipid and protein phosphatase activity of PTEN, respectively, activates Akt and inhibits extrasynaptic NMDAR activity and thereby protects against ischemic neuronal death in vitro and in vivo. Thus, our study reveals a dual neuroprotective mechanism by which Akt/Bad and extrasynaptic NMDARs are regulated via downregulation of two distinct PTEN phosphatase activities and present the possibility of PTEN as a potential therapeutic target for stroke treatment. [ABSTRACT FROM AUTHOR]