Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia (MG) that activate the gene encoding proneural factor Achaete-scute homolog 1 (Ascl1; also known as Mash1 in mammals) and de-differentiate into progenitor cells. By contrast, mammalian MG limited regenerative response fail upregulate Ascl1 after injury. To test whether ASCL1 could restore neurogenic potential MG, we overexpressed dissociated mouse cultures intact explants. ASCL1-infected...

Cannabinoids, the active constituents of marijuana, are known to impair learning and memory. Receptors for cannabinoids highly expressed in hippocampus, a brain region that is believed play an important role certain forms To investigate possible contribution cannabinoid receptor-mediated deficits hippocampal function memory impairments produced by we studied effects receptor activation on two models memory, long-term potentiation (LTP) depression (LTD), slices. Although LTP LTD CA1 field...

We report a thorough analysis of neurotransmission in cultured hippocampal neurons lacking synaptic vesicle protein 2 (SV2), membrane glycoprotein present all vesicles that undergo regulated secretion. found SV2 selectively enhances low-frequency by priming morphologically docked vesicles. Loss reduced initial release probability during train action potentials but had no effect on steady-state responses. The amount and decay rate asynchronous release, two measures sensitive to presynaptic...

GLT-1, the major glutamate transporter in adult brain, is abundantly expressed astrocytic processes enveloping synapses. By limiting escape into surrounding neuropil, GLT-1 preserves spatial specificity of synaptic signaling. Here we show that amyloid-β peptide Aβ 1–42 markedly prolongs extracellular lifetime synaptically released by reducing surface expression mouse astrocytes and this effect prevented vitamin E derivative Trolox. These findings indicate dysfunction may play an important...

Cannabinoids, such as marijuana, are known to impair learning and memory perhaps through their actions in the hippocampus where cannabinoid receptors expressed at high density. Although receptor activation decreases glutamatergic synaptic transmission cultured hippocampal neurons, mechanisms of this action not known. Cannabinoid also inhibits calcium channels that support neurotransmitter release these cells, making modulation a candidate for cannabinoid-receptor-mediated effects on...

In the rat central nervous system, mRNA encoding N-methyl-D-aspartate receptor subunit R1 is most ubiquitously distributed among cloned mRNAs of this glutamate subtype. The very abundantly expressed and coexpression necessary for functional expression all other subunits. Therefore, likely to be an essential component known receptors in brain. By employing sequence specific polyclonal antibodies, we demonstrate that brain R1, as well recombinantly protein, has apparent molecular mass 116 kDa...

Overexpression of the amyloid precursor protein (APP) in hippocampal neurons leads to elevated beta-amyloid peptide (Abeta) production and consequent depression excitatory transmission. The precise mechanisms underlying APP-induced synaptic are poorly understood. Uncovering these could provide insight into how neuronal function is compromised before cell death during early stages Alzheimer's disease. Here we verify that APP up-regulation transmission cultured autapses; perform whole-cell...

MicroRNAs play important regulatory roles in a broad range of cellular processes including neuronal morphology and long-term synaptic plasticity. MicroRNA-132 (miR132) is CREB-regulated miRNA that induced by activity neurotrophins, plays role regulating excitability. Little known about the effects miR132 expression on function. Here we show overexpression increases paired-pulse ratio decreases depression cultured mouse hippocampal neurons without affecting initial probability...

Presynaptic receptors that are coupled to heterotrimeric G-proteins found throughout the brain and responsible for modulating synaptic transmission. At least 10 G-protein-coupled (GPCRs) reduce transmission in hippocampal neurons. Additionally, neurons express up 17 different Gα, Gβ, Gγ subunits, making a striking array of possible heterotrimer compositions GPCR–heterotrimer interactions. The identity Gα subunit is likely critical determinant coupling specificity between GPCRs their...

Significance Information processing in the brain is mediated through synaptic connections between neurons, where neurotransmitter molecules released from presynaptic nerve terminals stimulate postsynaptic cells. Strength of transmission increased transiently by short-term facilitation response to repeated stimulation fibers. Synaptic initiated calcium influx channels terminals, which are regulated sensor proteins. We found that genetically modified mice we introduced a mutation binding site...

Synaptotagmin IV (Syt IV) is a brain-specific isoform of the synaptotagmin family, levels which are strongly elevated after seizure activity. The dominant hypothesis Syt function states that upregulation neuroprotective mechanism for reducing neurotransmitter release. To test this in mammalian CNS synapses, was overexpressed cultured mouse hippocampal neurons, and acute effects on fast excitatory neurotransmission were assessed. We found unaltered with respect to basal release probability,...

With a multitude of substrates, γ-secretase is poised to control neuronal function through variety signaling pathways. Presenilin 1 (PS1) an integral component and also protein closely linked the etiology Alzheimer's disease (AD). To better understand roles PS1 in normal pathological synaptic transmission, we examined evoked spontaneous neurotransmitter release cultured hippocampal neurons derived from knock-out (KO) mice. We found no changes size currents, short-term plasticity, or apparent...

To evaluate real-world pharmacologic treatment of mixed dyslipidemia in patients with diabetes mellitus (DM). All commercial health plan members a large US managed care database complete lipid panel results (HDL-C, LDL-C, TG) between 1/1/2006 and 12/31/2006 were identified (N = 529,236). DM 53,679) defined as having any 2 suboptimal parameters 28,728). Lipid status 6 months pre- post-index date was determined using pharmacy claims for therapy. Post-index, 41.1% abnormal 45.1% 3 did not...

Background:Thrombocytopenia is a significant risk for patients with chronic HCV infection and common side-effect of treatment pegylated (PEG) interferon (IFN). Thrombocytopenia predisposes to bleeding requirements platelet transfusions, may thus place an increased burden on medical resource utilisation.Scope:In retrospective analysis integrated, longitudinal database pharmacy claims laboratory results in US commercial health (insurance) plan, hepatitis C viral (HCV) were identified by...

Abstract Objective To identify the association between insulin out‐of‐pocket costs (OOPC) and adherence to in Medicare Advantage (MA) patients. Data Sources Study Setting The study is based on Optum Labs Warehouse, a longitudinal, real‐world data asset with de‐identified administrative claims electronic health record data. Design Using descriptive multivariable logistic regression analyses, we identified likelihood of patients diabetes having ≥60 consecutive days an expected fill date actual...