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Astrocyte-mediated short-term synaptic depression in the rat hippocampal CA1 area : two modes of decreasing release probability

BACKGROUND: Synaptic burst activation feeds back as a short-term depression of release probability at hippocampal CA3-CA1 synapses. This short-term synaptic plasticity requires functional astrocytes and it affects both the recently active (< 1 s) synapses (post-burst depression) as well as inactive neighboring synapses (transient heterosynaptic depression). The aim of this study was to investigate

Astrocytes impose postburst depression of release probability at hippocampal glutamate synapses

Many neurons typically fire action potentials in brief, high-frequency bursts with specific consequences for their synaptic output. Here we have examined short-term plasticity engaged during burst activation using electrophysiological recordings in acute rat hippocampal slices. We show that CA3-CA1 glutamate synapses exhibit a prominent depression of presynaptic release probability for approximate

Synaptic retrogenesis and amyloid-beta in Alzheimer's disease

Pathological hallmarks of Alzheimer's disease (AD) include synaptic and neuronal degeneration and the presence of extracellular deposits of amyloid-beta (Abeta) in senile plaques in the cerebral cortex. Although these brain lesions may be seen also in aged non-demented individuals, the increase in brain Abeta is believed by many to represent the earliest event in the disease process. Accumulating

Astrocytes play a critical role in transient heterosynaptic depression in the rat hippocampal CA1 region

Active synapses can reduce the probability of transmitter release at neighbouring synapses. Depending on whether such heterosynaptic depression is mediated by intersynaptic diffusion of transmitter or by release of gliotransmitters, astrocytes should either hinder or promote the heterosynaptic depression. In the present study we have examined the developmental profile and astrocytic involvement in

Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function

A major challenge in neuroscience is to resolve the connection between gene functionality, neuronal circuits, and behavior. Most, if not all, neuronal circuits of the adult brain contain a glutamatergic component, the nature of which has been difficult to assess because of the vast cellular abundance of glutamate. In this study, we wanted to determine the role of a restricted subpopulation of glut

Examining drivers of sustainable consumption : The influence of norms and opinion leadership on electric vehicle adoption in Sweden

Transportation accounts for a large and growing part of carbon dioxide emissions. With an increasing vehicle fleet worldwide private car use is becoming an acute problem in need of urgent attention and action. Policy interference and cleaner cars are not enough; alternative fuel vehicles such as electric vehicles need to be adopted by consumers as well. Previous research on pro-environmental consu

A Collective Picture of What Makes People Happy: Words Representing Social Relationships, not Money, are Recurrent with the Word ‘Happiness’

The Internet allows people to freely navigate through news and use that information to reinforce or support their own beliefs in, for example, different social networks. In this chapter we suggest that the representation of current predominant views in the news can be seen as collective expressions within a society. Seeing that the notion of what makes individuals happy has been of increasing inte

Deletion of the mitochondrial chaperone TRAP-1 uncovers global reprogramming of metabolic networks

Reprogramming of metabolic pathways contributes to human disease, especially cancer, but the regulators of this process are unknown. Here, we have generated a mouse knockout for the mitochondrial chaperone TRAP-1, a regulator of bioenergetics in tumors. TRAP-1(-/-) mice are viable and showed reduced incidence of age-associated pathologies, including obesity, inflammatory tissue degeneration, dyspl

DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin

DNA-dependent protein kinase (DNA-PK) plays a key role in the repair of DNA double-strand breaks (DSBs) that are probably the most deleterious form of DNA damage. Inhibition of DNA-PK has been considered as an attractive approach to decrease resistance to therapeutically induced DNA DSBs. Ionizing radiation (IR) and doxorubicin, which induce DSBs, are used in the treatment of breast cancer. We det

Cyclophilin D extramitochondrial signaling controls cell cycle progression and chemokine-directed cell motility

Mitochondria control bioenergetics and cell fate decisions, but how they influence nuclear gene expression is understood poorly. Here, we show that deletion or reduction in the levels of cyclophilin D (CypD, also called Ppif), a mitochondrial matrix peptidyl prolyl isomerase and apoptosis regulator, results in increased cell proliferation and enhanced cell migration and invasion. These responses a

Chk2 phosphorylation of survivin-DeltaEx3 contributes to a DNA damage-sensing checkpoint in cancer

Survivin is an oncogene that functions in cancer cell cytoprotection and mitosis. Here we report that differential expression in cancer cells of a C-terminal splice variant of survivin, termed survivin-ΔEx3, is tightly associated with aggressive disease and markers of unfavorable prognosis. In contrast to other survivin variants, survivin-ΔEx3 localized exclusively to nuclei in tumor cells and was

Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K

DNA double-strand breaks (DSB) are the most cytotoxic lesions induced by topoisomerase II poisons. Nonhomologous end joining (NHEJ) is a major pathway for DSB repair and requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK catalytic subunit (DNA-PKcs) is structurally similar to PI-3K, which promotes cell survival and proliferation and is upregulated in many cancers. KU-0060648 is a dual

Further characterisation of the cellular activity of the DNA-PK inhibitor, NU7441, reveals potential cross-talk with homologous recombination

PURPOSE: Inhibition of DNA repair is emerging as a new therapeutic strategy for cancer treatment. One promising target is DNA-PK, a pivotal kinase in double-strand break repair. The purpose of this study was to further characterise the activity of the DNA-PK inhibitor NU7441, giving some new insights into the biology of DNA-PK.METHODS: We used NU7441, a potent DNA-PK inhibitor, to evaluate potenti

Targeted inhibition of mitochondrial Hsp90 suppresses localised and metastatic prostate cancer growth in a genetic mouse model of disease

BACKGROUND: The molecular chaperone heat shock protein-90 (Hsp90) is a promising cancer drug target, but current Hsp90-based therapy has so far shown limited activity in the clinic.METHODS: We tested the efficacy of a novel mitochondrial-targeted, small-molecule Hsp90 inhibitor, Gamitrinib (GA mitochondrial matrix inhibitor), in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. Th