scholarly journals F-actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes

2019 ◽  
Author(s):  
Bas van Bommel ◽  
Anja Konietzny ◽  
Oliver Kobler ◽  
Julia Bär ◽  
Marina Mikhaylova
Keyword(s):  
Actin Cytoskeleton ◽  
Organelle Transport ◽  
Strong Impact ◽  
Neuronal Function ◽  
Glutamatergic Synapses ◽  
Dendritic Shaft ◽  
Myosin Va ◽  
Organelle Trafficking ◽  
Shaft Synapses

AbstractOrganelle positioning within neurites is required for proper neuronal function. In dendrites with their complex cytoskeletal organization, transport of organelles is guided by local specializations of the microtubule and actin cytoskeleton, and by coordinated activity of different motor proteins. Here, we focus on the actin cytoskeleton in the dendritic shaft and describe dense structures consisting of longitudinal and branched actin filaments. These actin patches are devoid of microtubules and are frequently located at the base of spines, or form an actin mesh around excitatory shaft synapses. Using lysosomes as an example, we demonstrate that the presence of actin patches has a strong impact on dendritic organelle transport, as lysosomes frequently stall at these locations. We provide mechanistic insights on this pausing behavior, demonstrating that actin patches form a physical barrier for kinesin-driven cargo. In addition, we identify myosin Va as an active tether which mediates long-term stalling. This correlation between the presence of actin meshes and halting of organelles could be a generalized principle by which synapses control organelle trafficking.

025 Sleep Disruption on an Orbital Shaker alters Glutamate in Prairie Vole Prefrontal Cortex

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A11-A12
Author(s):  
Carolyn Jones ◽  
Randall Olson ◽  
Alex Chau ◽  
Peyton Wickham ◽  
Ryan Leriche ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Prefrontal Cortex ◽  
Early Life ◽  
Autism Spectrum ◽  
Prairie Vole ◽  
Sleep Disruption ◽  
Glutamatergic Synapses ◽  
The Brain ◽  
Orbital Shaker

Abstract Introduction Glutamate concentrations in the cortex fluctuate with the sleep wake cycle in both rodents and humans. Altered glutamatergic signaling, as well as the early life onset of sleep disturbances have been implicated in neurodevelopmental disorders such as autism spectrum disorder. In order to study how sleep modulates glutamate activity in brain regions relevant to social behavior and development, we disrupted sleep in the socially monogamous prairie vole (Microtus ochrogaster) rodent species and quantified markers of glutamate neurotransmission within the prefrontal cortex, an area of the brain responsible for advanced cognition and complex social behaviors. Methods Male and female prairie voles were sleep disrupted using an orbital shaker to deliver automated gentle cage agitation at continuous intervals. Sleep was measured using EEG/EMG signals and paired with real time glutamate concentrations in the prefrontal cortex using an amperometric glutamate biosensor. This same method of sleep disruption was applied early in development (postnatal days 14–21) and the long term effects on brain development were quantified by examining glutamatergic synapses in adulthood. Results Consistent with previous research in rats, glutamate concentration in the prefrontal cortex increased during periods of wake in the prairie vole. Sleep disruption using the orbital shaker method resulted in brief cortical arousals and reduced time in REM sleep. When applied during development, early life sleep disruption resulted in long-term changes in both pre- and post-synaptic components of glutamatergic synapses in the prairie vole prefrontal cortex including increased density of immature spines. Conclusion In the prairie vole rodent model, sleep disruption on an orbital shaker produces a sleep, behavioral, and neurological phenotype that mirrors aspects of autism spectrum disorder including altered features of excitatory neurotransmission within the prefrontal cortex. Studies using this method of sleep disruption combined with real time biosensors for excitatory neurotransmitters will enhance our understanding of modifiable risk factors, such as sleep, that contribute to the altered development of glutamatergic synapses in the brain and their relationship to social behavior. Support (if any) NSF #1926818, VA CDA #IK2 BX002712, Portland VA Research Foundation, NIH NHLBI 5T32HL083808-10, VA Merit Review #I01BX001643

scholarly journals Central Insulin Signaling Is Attenuated by Long-Term Insulin Exposure via Insulin Receptor Substrate-1 Serine Phosphorylation, Proteasomal Degradation, and Lysosomal Insulin Receptor Degradation

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Christopher M. Mayer ◽  
Denise D. Belsham
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Time Course ◽  
Proteasomal Degradation ◽  
Serine Phosphorylation ◽  
Neuronal Function ◽  
Protein Levels ◽  
Phosphorylated Akt

Abstract Central insulin signaling is critical for the prevention of insulin resistance. Hyperinsulinemia contributes to insulin resistance, but it is not yet clear whether neurons are subject to cellular insulin resistance. We used an immortalized, hypothalamic, clonal cell line, mHypoE-46, which exemplifies neuronal function and expresses the components of the insulin signaling pathway, to determine how hyperinsulinemia modifies neuronal function. Western blot analysis indicated that prolonged insulin treatment of mHypoE-46 cells attenuated insulin signaling through phospho-Akt. To understand the mechanisms involved, time-course analysis was performed. Insulin exposure for 4 and 8 h phosphorylated Akt and p70-S6 kinase (S6K1), whereas 8 and 24 h treatment decreased insulin receptor (IR) and IR substrate 1 (IRS-1) protein levels. Insulin phosphorylation of S6K1 correlated with IRS-1 ser1101 phosphorylation and the mTOR-S6K1 pathway inhibitor rapamycin prevented IRS-1 serine phosphorylation. The proteasomal inhibitor epoxomicin and the lysosomal pathway inhibitor 3-methyladenine prevented the degradation of IRS-1 and IR by insulin, respectively, and pretreatment with rapamycin, epoxomicin, or 3-methyladenine prevented attenuation of insulin signaling by long-term insulin exposure. Thus, a sustained elevation of insulin levels diminishes neuronal insulin signaling through mTOR-S6K1-mediated IRS-1 serine phosphorylation, proteasomal degradation of IRS-1 and lysosomal degradation of the IR.

Contrasting Perspectives Regarding Climate Risks and Adaptation Strategies in the New York Metropolitan Area after Superstorm Sandy

2014 ◽  
Vol 01 (01) ◽  
pp. 1450005 ◽  
Author(s):  
Stephanie Miller ◽  
Griffin Kidd ◽  
Franco Montalto ◽  
Patrick Gurian ◽  
Cortney Worrall ◽  
...  
Keyword(s):  
Climate Change ◽  
New York ◽  
Adaptation Strategies ◽  
Mitigation Strategies ◽  
Strong Impact ◽  
Structured Interviews ◽  
Superstorm Sandy ◽  
Climate Risks ◽  
York Metropolitan Area

The purpose of this study was to examine stakeholder perceptions of climate change and local adaptation strategies in the New York City area. A side-by-side comparison of expert and resident opinions provided a clear picture of the region's climate change attitude in the year following Superstorm Sandy. Semi-structured interviews with regional environmental experts provided material for a structured survey, which was then distributed to 100 experts and 250 residents in coastal NY and northern NJ counties. In the survey both stakeholder groups were asked to choose the top three climate threats to the NYC region and rate adaptation and mitigation strategies on a 1–5 Likert scale regarding their ability to protect the region and their cost-effectiveness. Results show that experts and residents agree that sea level rise, coastal flooding and storm surge, and an increased frequency and intensity of extreme events pose the greatest threats to NYC over the next 25 years. While both groups showed a preference for long-term planning over immediate action, experts and residents could not agree on which specific strategies would best serve the region. The aftermath of Superstorm Sandy had a strong impact on both the expert and resident opinions and efforts to monitor stakeholder opinions continue.

scholarly journals Short‐term blood pressure changes have a more strong impact on stroke and its subtypes than long‐term blood pressure changes

2019 ◽  
Vol 42 (10) ◽  
pp. 925-933
Author(s):  
Rongrong Guo ◽  
Yanxia Xie ◽  
Jia Zheng ◽  
Yali Wang ◽  
Yue Dai ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Strong Impact ◽  
Short Term ◽  
Pressure Changes

Formation of stable microspikes containing actin and the 55 kDa actin bundling protein, fascin, is a consequence of cell adhesion to thrombospondin-1: implications for the anti-adhesive activities of thrombospondin-1

1995 ◽  
Vol 108 (5) ◽  
pp. 1977-1990 ◽  
Author(s):  
J.C. Adams
Keyword(s):  
Hydrogen Peroxide ◽  
Actin Cytoskeleton ◽  
Adherent Cells ◽  
Perinuclear Region ◽  
Adhesive Properties ◽  
Focal Contacts ◽  
Thrombospondin 1 ◽  
Indirect Immunofluorescence Staining ◽  
In Cells

The organisation of the actin cytoskeleton was examined in H9c2 and human intestinal smooth muscle cells adherent on fibronectin or thrombospondin-1. Whereas cells adherent on fibronectin adopted a polygonal shape and rapidly assembled prominent stress fibres and focal contacts, cells adherent on thrombospondin-1 assumed a more irregular morphology with large lamellae containing radial actin microspikes. Focal contacts were not detected in cells adherent on thrombospondin-1, as determined by indirect immunofluorescence staining for vinculin and other focal contact components. Instead, the radial microspikes stained positively for the actin-bundling protein, 55 kDa/fascin, and myosins. In cells adherent on fibronectin, 55 kDa/fascin immunoreactivity was diffuse and tended to be concentrated in the perinuclear region. In long-term adherent cells cultured in serum-containing medium, 55 kDa/fascin was detected in membrane ruffles, in stress fibres and in the perinuclear region. The microspikes formed within 40 minutes of plating cells on thrombospondin-1 and remained present when cells were treated with sodium orthovandate and hydrogen peroxide to increase intracellular phosphotyrosine levels. Indeed, although vanadate-treated cells tended to retract, the microspikes became more prominent and showed an increased intensity of staining for fascin. Under these conditions, a proportion of the microspikes did not appear to be in contact with the substratum: these spikes stained weakly for focal adhesion kinase, talin and vinculin. Cells treated with genistein also spread and formed fascin-containing microspikes which tended to be more slender than those of control cells. In contrast, cells adherent on fibronectin displayed a complex rearrangement of the actin cytoskeleton and a transient enrichment of 55 kDa/fascin-containing structures at the cell surface when treated with sodium orthovanadate and hydrogen peroxide. These observations indicate that cell interactions with fibronectin or thrombospondin-1 send distinct organisational signals to the actin cytoskeleton and may offer a mechanistic framework for further investigations of the anti-adhesive properties of thrombospondin-1.

Foreign Direct Investment (FDI) in Agriculture Implication into Emerging Country Change and Socio-Economic Development

2019 ◽  
pp. 28-38
Keyword(s):  
Foreign Direct Investment ◽  
Poverty Alleviation ◽  
Direct Investment ◽  
Job Creation ◽  
Strong Impact ◽  
Transfer Of Knowledge ◽  
Face To Face ◽  
Economy Growth ◽  
Agriculture Development

Foreign direct investment (FDI) has been used as a strategy in emerging countries which made a tremendous change in their economy. However, lack of study have been undertaken to know how these change can have contributed the country poverty alleviation and economy growth. Therefore, looking to fulfil the research gap, this paper aimed to seek how FDI implication in agriculture development through as job creation, taxes payment, transfer of knowledge and technology contribute the country poverty alleviation. The Lao People's Democratic Republic was used as a case study and a sample of 450 respondents were collected through a survey questionnaire by self-administrated (face to face with interaction with the participant). The results shown that FDI implication in agriculture development through FDI job creation, FDI taxes payment have a strong impact on poverty alleviation but with weak effect at long-term, however, FDI transfer of knowledge and technology have a weak impact on poverty alleviation though with greater significance at long term. Transfer of knowledge and technology is the significant asset needed for emerging economy from FDI to boost change and contribute to their economy growth.

scholarly journals Mechanisms Underlying Long-Term Synaptic Zinc Plasticity at Mouse Dorsal Cochlear Nucleus Glutamatergic Synapses

2020 ◽  
Vol 40 (26) ◽  
pp. 4981-4996 ◽  
Author(s):  
Nathan W. Vogler ◽  
Vincent M. Betti ◽  
Jacob M. Goldberg ◽  
Thanos Tzounopoulos
Keyword(s):  
Cochlear Nucleus ◽  
Dorsal Cochlear Nucleus ◽  
Glutamatergic Synapses

scholarly journals Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Signal Molecule ◽  
Brain Functions ◽  
Dendritic Shaft ◽  
Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

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