scholarly journals Metal Toxicity at the Synapse: Presynaptic, Postsynaptic, and Long-Term Effects

2012 ◽  
Vol 2012 ◽  
pp. 1-42 ◽  
Author(s):  
Sanah Sadiq ◽  
Zena Ghazala ◽  
Arnab Chowdhury ◽  
Dietrich Büsselberg
Keyword(s):  
Synaptic Plasticity ◽  
Gaba Receptors ◽  
Intracellular Signaling ◽  
Health Concern ◽  
Metal Species ◽  
Long Term Effects ◽  
Metal Interactions ◽  
Intracellular Signaling Pathways ◽  
Specific Metal

Metal neurotoxicity is a global health concern. This paper summarizes the evidence for metal interactions with synaptic transmission and synaptic plasticity.Presynapticallymetal ions modulate neurotransmitter release through their interaction with synaptic vesicles, ion channels, and the metabolism of neurotransmitters (NT). Many metals (e.g., , , and ) also interact with intracellular signaling pathways.Postsynaptically, processes associated with the binding of NT to their receptors, activation of channels, and degradation of NT are altered by metals. , , , , , , , , and methylmercury modulate NMDA, AMPA/kainate, and/or GABA receptors activity. , , , and also impairsynaptic plasticityby targeting molecules such as CaM, PKC, and NOS as well as the transcription machinery involved in the maintenance of synaptic plasticity. The multiple effects of metals might occur simultaneously and are based on the specific metal species, metal concentrations, and the types of neurons involved.

scholarly journals Intermittent and Periodic Fasting, Hormones, and Cancer Prevention

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4587
Author(s):  
Giulia Salvadori ◽  
Mario Giuseppe Mirisola ◽  
Valter D. Longo
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Intracellular Signaling ◽  
Cellular Damage ◽  
Long Term Effects ◽  
Dietary Interventions ◽  
Genetic Pathways ◽  
Intracellular Signaling Pathways ◽  
Preventive Effects

The restriction of proteins, amino acids or sugars can have profound effects on the levels of hormones and factors including growth hormone, IGF-1 and insulin. In turn, these can regulate intracellular signaling pathways as well as cellular damage and aging, but also multisystem regeneration. Both intermittent (IF) and periodic fasting (PF) have been shown to have both acute and long-term effects on these hormones. Here, we review the effects of nutrients and fasting on hormones and genes established to affect aging and cancer. We describe the link between dietary interventions and genetic pathways affecting the levels of these hormones and focus on the mechanisms responsible for the cancer preventive effects. We propose that IF and PF can reduce tumor incidence both by delaying aging and preventing DNA damage and immunosenescence and also by killing damaged, pre-cancerous and cancer cells.

scholarly journals Long-term effects of increased adoption of artemisinin combination therapies in Burkina Faso

2021 ◽  
Author(s):  
Robert J. Zupko ◽  
Tran Dang Nguyen ◽  
Anyirékun Fabrice Somé ◽  
Thu Nguyen-Anh Tran ◽  
Jaline Gerardin ◽  
...  
Keyword(s):  
Burkina Faso ◽  
De Novo ◽  
Health Concern ◽  
Combination Therapies ◽  
Long Term Effects ◽  
First Line ◽  
Private Market ◽  
Resistant Genotypes ◽  
Artemisinin Combination Therapies

AbstractArtemisinin combination therapies (ACTs) are the WHO-recommended first-line therapies for uncomplicated Plasmodium falciparum malaria. The emergence and spread of artemisinin-resistant genotypes is a major global public health concern. To explore how the increased adoption of ACTs may affect the high-burden high-impact malaria setting of Burkina Faso, we added spatial structure to a validated individual-based stochastic model of P. falciparum transmission and evaluated long-term effects of increased ACT use. We explored how de novo emergence of artemisinin-resistant genotypes may occur under scenarios in which private-market drugs are eliminated or multiple first-line therapies (MFT) are deployed. We found that elimination of private market drugs would reduce the long-run treatment failures. An MFT policy with equal deployment of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) may accelerate near-term drug resistance and treatment failure rates, due to early failure and substantially reduced treatment efficacy resulting from piperaquine-resistant genotypes. A rebalanced MFT approach (90% AL, 10% DHA-PPQ) results in better long-term outcomes than using AL alone but may be difficult to implement in practice.

scholarly journals Neuroinflammatory Triangle Presenting Novel Pharmacological Targets for Ischemic Brain Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaib A. Shaheryar ◽  
Mahtab A. Khan ◽  
Ch. Sherjeel Adnan ◽  
Awais Ali Zaidi ◽  
Daniel Hänggi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracellular Signaling ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Post Stroke ◽  
Intracellular Signaling Pathways ◽  
Pharmacological Targets ◽  
Specific Receptors ◽  
Ros Burst

Ischemic stroke is one of the leading causes of morbidity and mortality globally. Hundreds of clinical trials have proven ineffective in bringing forth a definitive and effective treatment for ischemic stroke, except a myopic class of thrombolytic drugs. That, too, has little to do with treating long-term post-stroke disabilities. These studies proposed diverse options to treat stroke, ranging from neurotropic interpolation to venting antioxidant activity, from blocking specific receptors to obstructing functional capacity of ion channels, and more recently the utilization of neuroprotective substances. However, state of the art knowledge suggests that more pragmatic focus in finding effective therapeutic remedy for stroke might be targeting intricate intracellular signaling pathways of the ‘neuroinflammatory triangle’: ROS burst, inflammatory cytokines, and BBB disruption. Experimental evidence reviewed here supports the notion that allowing neuroprotective mechanisms to advance, while limiting neuroinflammatory cascades, will help confine post-stroke damage and disabilities.

scholarly journals VEGF-A and ICAM-1 Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer

2019 ◽  
Vol 20 (22) ◽  
pp. 5791 ◽  
Author(s):  
Apostolos Papachristos ◽  
Polychronis Kemos ◽  
Theodora Katsila ◽  
Eirini Panoilia ◽  
George P. Patrinos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
First Line ◽  
Intracellular Signaling Pathways

Bevacizumab is used to treat metastatic colorectal cancer (mCRC). However, there are still no available predictors of clinical outcomes. We investigated selected single nucleotide polymorphisms (SNPs) in the genes involved in VEGF-dependent and -independent angiogenesis pathways and other major intracellular signaling pathways involved in the pathogenesis of mCRC as an attempt to find predictors of clinical outcome. Forty-six patients treated with first-line bevacizumab-based chemotherapy were included in this study with a 5 year follow up. Genomic DNA was isolated from whole blood for the analysis of VEGF-A (rs2010963, 1570360, rs699947), ICAM-1 (rs5498, rs1799969) SNPs and from tumor tissue for the detection of genomic variants in KRAS, NRAS, BRAF genes. PCR and next generation sequencing were used for the analysis. The endpoints of the study were progression-free survival (PFS) and overall survival (OS). The VEGF-A rs699947 A/A allele was associated with increased PFS (p = 0.006) and OS (p = 0.043). The ICAM-1 rs1799969 G/A allele was associated with prolonged OS (p = 0.036). Finally, BRAF wild type was associated with increased OS (p = 0.027). We identified VEGF-A and ICAM-1 variants in angiogenesis and other major intracellular signaling pathways, such as BRAF, that can predict clinical outcome upon bevacizumab administration. These identified biomarkers could be used to select patients with mCRC who may achieve long-term responses and benefit from bevacizumab-based therapies.

scholarly journals Environmental Enrichment Rescues Endocannabinoid-Dependent Synaptic Plasticity Lost in Young Adult Male Mice after Ethanol Exposure during Adolescence

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 825
Author(s):  
Irantzu Rico-Barrio ◽  
Sara Peñasco ◽  
Leire Lekunberri ◽  
Maitane Serrano ◽  
Jon Egaña-Huguet ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Metabotropic Glutamate Receptors ◽  
Transient Receptor Potential ◽  
Long Term Potentiation ◽  
Perforant Path ◽  
Health Concern ◽  
Adolescent Male ◽  
Transient Receptor Potential Vanilloid ◽  
Group I

Binge drinking (BD) is a serious health concern in adolescents as high ethanol (EtOH) consumption can have cognitive sequelae later in life. Remarkably, an enriched environment (EE) in adulthood significantly recovers memory in mice after adolescent BD, and the endocannabinoid, 2-arachydonoyl-glycerol (2-AG), rescues synaptic plasticity and memory impaired in adult rodents upon adolescent EtOH intake. However, the mechanisms by which EE improves memory are unknown. We investigated this in adolescent male C57BL/6J mice exposed to a drinking in the dark (DID) procedure four days per week for a duration of 4 weeks. After DID, the mice were nurtured under an EE for 2 weeks and were subjected to the Barnes Maze Test performed the last 5 days of withdrawal. The EE rescued memory and restored the EtOH-disrupted endocannabinoid (eCB)-dependent excitatory long-term depression at the dentate medial perforant path synapses (MPP-LTD). This recovery was dependent on both the cannabinoid CB1 receptor and group I metabotropic glutamate receptors (mGluRs) and required 2-AG. Also, the EE had a positive effect on mice exposed to water through the transient receptor potential vanilloid 1 (TRPV1) and anandamide (AEA)-dependent MPP long-term potentiation (MPP-LTP). Taken together, EE positively impacts different forms of excitatory synaptic plasticity in water- and EtOH-exposed brains.

scholarly journals Long-Term Shaping of Corticostriatal Synaptic Activity by Acute Fasting

2021 ◽  
Vol 22 (4) ◽  
pp. 1916
Author(s):  
Federica Campanelli ◽  
Daniela Laricchiuta ◽  
Giuseppina Natale ◽  
Gioia Marino ◽  
Valeria Calabrese ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Food Deprivation ◽  
Physiological State ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Synaptic Activity ◽  
Striatal Neurons ◽  
Long Term Effects ◽  
Salient Event

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes. Despite an increasing number of studies pointing towards specific changes in response to dietary restrictions in brain regions, such as the nucleus accumbens and hippocampus, none have investigated the long-term effects of such practice in the dorsal striatum. This basal ganglia nucleus is involved in habit formation and in eating behavior, especially that based on dopaminergic control of motivation for food in both humans and animals. Here, we explored whether we could retrieve long-term signs of changes in AMPARs subunit composition in dorsal striatal neurons of mice acutely deprived for 12 hours/day for two consecutive days by analyzing glutamatergic neurotransmission and the principal forms of dopamine and glutamate-dependent synaptic plasticity. Overall, our data show that a moderate food deprivation in experimental animals is a salient event mirrored by a series of neuroadaptations and suggest that dietary restriction may be determinant in shaping striatal synaptic plasticity in the physiological state.

scholarly journals First long-term and near real-time measurement of atmospheric trace elements in Shanghai, China

2017 ◽  
Author(s):  
Yunhua Chang ◽  
Kan Huang ◽  
Congrui Deng ◽  
Zhong Zou ◽  
Shoudong Liu ◽  
...  
Keyword(s):  
Trace Elements ◽  
Fine Particles ◽  
Health Concern ◽  
Metal Species ◽  
Effective Control ◽  
Pollution Level ◽  
High Time Resolution ◽  
Long Distance ◽  
Stationary Combustion

Abstract. Atmospheric trace elements, especially metal species, are an emerging environmental and health concern with poorly constrained on its abundances and sources in Shanghai, the most important industrial megacity in China. Here we continuously performed a one-year (from March 2016 to February 2017) and hourly-resolved measurement of eighteen elements in fine particles (PM2.5) at Shanghai urban center with a Xact multi-metals monitor and several collocated instruments. Independent ICP-MS offline analysis of filter samples was used to validate the performance of Xact that was based on energy-dispersive X-ray fluorescence analysis of aerosol deposits on reactive filter tapes. Mass concentrations (mean ± 1σ; ng m-3) determined by Xact ranged from detection limits (nominally 0.1 to 20 ng m-3) to 14.7 µg m-3, with Si as the most abundant element (638.7 ± 1004.5), followed by Fe (406.2 ± 385.2), K (388.6 ± 326.4), Ca (191.5 ± 383.2), Zn (120.3 ± 131.4), Mn (31.7 ± 38.7), Pb (27.2 ± 26.1), Ba (24.2 ± 25.4), V (13.4 ± 14.5), Cu (12.0 ± 11.4), Cd (9.6 ± 3.9), As (6.6 ± 6.6), Ni (6.0 ± 5.4), Cr (4.5 ± 6.1), Ag (3.9 ± 2.6), Se (2.6 ± 2.9), Hg (2.2 ± 1.7), and Au (2.2 ± 3.4). Metal related oxidized species comprised an appreciable fraction of PM2.5 during all seasons, accounting for 8.3 % on average. As a comparison, atmospheric metal pollution level in Shanghai was comparable with other industrialized cities in East Asia but one or two orders magnitude higher than the sites in North America and Europe. Here our high time-resolution observations over long-term period also offer a unique opportunity to provide robust diurnal profiles for each species, which are useful in determining the sources and processes contributing to the fluctuation of atmospheric trace elements. Besides, various mathematical methods and physical evidences were served as criteria to constrain various solutions of source identification. Results showed that atmospheric trace elements pollution in Shanghai was the interplay of local emissions and regional transport, and different sources of metal species generally have different variation patterns associated with different source regions. Specifically, V and Ni were confirmed as the prominent and exclusive tracer of heavy oil combustion from shipping traffic. Fe and Ba were strongly related to brake wear, and exhibited significant correlation with Si and Ca, suggesting that Si and Ca in Shanghai were primarily sourced from road fugitive dust rather than long-distance dust transport and local building construction sites. Stationary combustion of coal was found to be the major source of As, Se, Pb, Cu and K, and the ratio of As / Se was used to infer that coal consumed in Shanghai likely originated from Henan coal fields in Northern China. Cr, Mn and Zn were the mixed result of emissions from stationary combustion coal, ferrous metals production, and nonferrous metals processing. Ag and Cd in Shanghai urban atmosphere were also the mixture of miscellaneous sources. Collectively, our findings in this study provide baseline data with high detail, which are needed for developing effective control strategies to reduce the high risk of acute exposure to atmospheric trace elements in China's megacities.

Distribution and Function of GABAB Receptors in Spider Peripheral Mechanosensilla

2003 ◽  
Vol 90 (4) ◽  
pp. 2571-2580 ◽  
Author(s):  
Izabela Panek ◽  
Shannon Meisner ◽  
Päivi H. Torkkeli
Keyword(s):  
Sensory Neurons ◽  
Glial Cells ◽  
Gaba Receptors ◽  
Synaptic Vesicles ◽  
Sensory Cell ◽  
Gabab Receptors ◽  
Long Term Effects ◽  
And Function ◽  
Receptor Antibodies

The mechanosensilla in spider exoskeleton are innervated by bipolar neurons with their cell bodies close to the cuticle and dendrites attached to it. Numerous efferent fibers synapse with peripheral parts of the mechanosensory neurons, with glial cells surrounding the neurons, and with each other. Most of these efferent fibers are immunoreactive to γ-aminobutyric acid (GABA), and the sensory neurons respond to agonists of ionotropic GABA receptors with a rapid and complete inhibition. In contrast, little is known about metabotropic GABAB receptors that may mediate long-term effects. We investigated the distribution of GABAB receptors on spider leg mechanosensilla using specific antibodies against 2 proteins needed to form functional receptors and an antibody that labels the synaptic vesicles on presynaptic sites. Both anti-GABAB receptor antibodies labeled the distal parts of the sensory cell bodies and dendrites but anti-GABABR1 immunoreactivity was also found in the axons and proximal parts of the cell bodies and some glial cells. The fine efferent fibers that branch on top of the sensory neurons did not show GABAB receptor immunoreactivity but were densely labeled with anti-synapsin and indicated synaptic vesicles on presynaptic locations to the GABAB receptors. Intracellular recordings from sensory neurons innervating the slit sensilla of the spider legs revealed that application of GABAB receptor agonists attenuated voltage-activated Ca2+ current and enhanced voltage-activated outward K+ current, providing 2 possible mechanisms for controlling the neurons' excitability. These findings support the hypothesis that GABAB receptors are present in the spider mechanosensilla where their activation may modulate information transmission.

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