Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits

AbstractCCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. The general excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor event in the cells’ whole transcriptome, can underlie distinct cell-type identity.

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Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits

eLife ◽

10.7554/elife.58515 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Viktor János Oláh ◽

David Lukacsovich ◽

Jochen Winterer ◽

Antónia Arszovszki ◽

Andrea Lőrincz ◽

...

Keyword(s):

Low Voltage ◽

Auxiliary Subunits ◽

Functional Specification ◽

Gene Profiles ◽

Hippocampal Activity ◽

Hippocampal Ca3 ◽

Underlying Mechanisms ◽

Firing Properties ◽

A Minor ◽

Whole Transcriptome

CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat hippocampal CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8–15 Hz oscillations. By contrast, the general intrinsic excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor change in the cells’ whole transcriptome, can determine cell-type identity.

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Congenital hypothyroidism impairs spine growth of dentate granule cells by downregulation of CaMKIV

Cell Death Discovery ◽

10.1038/s41420-021-00530-z ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Qingying Tang ◽

Shuxia Chen ◽

Hui Wu ◽

Honghua Song ◽

Yongjun Wang ◽

...

Keyword(s):

Congenital Hypothyroidism ◽

Granule Cells ◽

Spine Density ◽

Drug Induced ◽

Distinct Cell Type ◽

Cognitive Behaviors ◽

Dentate Granule Cells ◽

Rat Pups ◽

Cognitive Deficiency ◽

Underlying Mechanisms

AbstractCongenital hypothyroidism (CH), a common neonatal endocrine disorder, can result in cognitive deficits if delay in diagnose and treatment. Dentate gyrus (DG) is the severely affected subregion of the hippocampus by the CH, where the dentate granule cells (DGCs) reside in. However, how CH impairs the cognitive function via affecting DGCs and the underlying mechanisms are not fully elucidated. In the present study, the CH model of rat pups was successfully established, and the aberrant dendrite growth of the DGCs and the impaired cognitive behaviors were observed in the offspring. Transcriptome analysis of hippocampal tissues following rat CH successfully identified that calcium/calmodulin-dependent protein kinase IV (CaMKIV) was the prominent regulator involved in mediating deficient growth of DGC dendrites. CaMKIV was shown to be dynamically regulated in the DG subregion of the rats following drug-induced CH. Interference of CaMKIV expression in the primary DGCs significantly reduced the spine density of dendrites, while addition of T3 to the primary DGCs isolated from CH pups could facilitate the spine growth of dendrites. Insights into relevant mechanisms revealed that CH-mediated CaMKIV deficiency resulted in the significant decrease of phosphorylated CREB in DGCs, in association with the abnormality of dendrites. Our results have provided a distinct cell type in hippocampus that is affected by CH, which would be beneficial for the treatment of CH-induced cognitive deficiency.

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RyR1 exhibits lower gain of CICR activity than RyR3 in the SR: evidence for selective stabilization of RyR1 channel

AJP Cell Physiology ◽

10.1152/ajpcell.00395.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. C36-C45 ◽

Cited By ~ 27

Author(s):

Takashi Murayama ◽

Yasuo Ogawa

Keyword(s):

Binding Sites ◽

Skeletal Muscles ◽

Specific Activity ◽

Adenine Nucleotides ◽

Minor Effect ◽

Mammalian Skeletal Muscle ◽

Selective Stabilization ◽

Underlying Mechanisms ◽

A Minor

We showed that frog α-ryanodine receptor (α-RyR) had a lower gain of Ca2+-induced Ca2+ release (CICR) activity than β-RyR in sarcoplasmic reticulum (SR) vesicles, indicating selective “stabilization” of the former isoform (Murayama T and Ogawa Y. J Biol Chem 276: 2953–2960, 2001). To know whether this is also the case with mammalian RyR1, we determined [3H]ryanodine binding of RyR1 and RyR3 in bovine diaphragm SR vesicles. The value of [3H]ryanodine binding (B) was normalized by the number of maximal binding sites (Bmax), whereby the specific activity of each isoform was expressed. This B/Bmax expression demonstrated that ryanodine binding of individual channels for RyR1 was <15% that for RyR3. Responses to Ca2+, Mg2+, adenine nucleotides, and caffeine were not substantially different between in situ and purified isoforms. These results suggest that the gain of CICR activity of RyR1 is markedly lower than that of RyR3 in mammalian skeletal muscle, indicating selective stabilization of RyR1 as is true of frog α-RyR. The stabilization was partly eliminated by FK506 and partly by solubilization of the vesicles with CHAPS, each of which was additive to the other. In contrast, high salt, which greatly enhances [3H]ryanodine binding, caused only a minor effect on the stabilization of RyR1. None of the T-tubule components, coexisting RyR3, or calmodulin was the cause. The CHAPS-sensitive intra- and intermolecular interactions that are common between mammalian and frog skeletal muscles and the isoform-specific inhibition by FKBP12, which is characteristic of mammals, are likely to be the underlying mechanisms.

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Penicillium simplicissimum NL-Z1 Induced an Imposed Effect to Promote the Leguminous Plant Growth

Frontiers in Microbiology ◽

10.3389/fmicb.2021.738734 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiayao Zhuang ◽

Chao Liu ◽

Xiaoxue Wang ◽

Tongxin Xu ◽

Hao Yang

Keyword(s):

Plant Growth ◽

Rock Slope ◽

Plant Biomass ◽

Control Treatment ◽

Leguminous Plant ◽

Penicillium Simplicissimum ◽

Nodule Biomass ◽

Underlying Mechanisms ◽

Phosphate Solubilizing ◽

A Minor

It is found effective for phytoremediation of the guest soil spraying method by adding microbes to promote the growth of arbor leguminous plant on a high and steep rock slope. However, its underlying mechanisms remain elusive. Here, some experiments were conducted to explore the multifunctions of Penicillium simplicissimum NL-Z1 on rock weathering, nodule growth, and beneficial microbial regulation. The results show that P. simplicissimum NL-Z1 significantly increased the release of phosphorus, potassium, calcium, and magnesium from the rock by 226, 29, 24, and 95%, respectively, compared with that of the control. A significant increase of 153% in Indigofera pseudotinctoria Matsum nodule biomass, accompanied by an increase of 37% in the leguminous plant biomass was observed in the P. simplicissimum NL-Z1 treatment than in the control treatment. Interestingly, even though P. simplicissimum NL-Z1 itself became a minor microbial community in the soil, it induced a significant increase in Mortierella, which, as a beneficial microbe, can promote phosphate-solubilizing and plant growth. The results suggest that P. simplicissimum NL-Z1 could induce an imposed effect to promote leguminous plant growth, which may be conducive to the development of the phytoremediation technique for high and steep rock slope. The study provides a novel thought of using the indirect effect of microbes, i.e., promoting other beneficial microbes, to improve soil environment.

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SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

Journal of Clinical Medicine ◽

10.3390/jcm10153441 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3441

Author(s):

Hashir Ali Awan ◽

Mufaddal Najmuddin Diwan ◽

Alifiya Aamir ◽

Muneeza Ali ◽

Massimo Di Giannantonio ◽

...

Keyword(s):

Olfactory Pathway ◽

Cognitive Sequelae ◽

Significant Burden ◽

Inflammatory State ◽

Underlying Mechanisms ◽

Acute Changes ◽

A Minor

The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual’s overall wellbeing, including adequate cognitive functioning. ‘Cognitive COVID’ is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of ‘Cognitive COVID’ as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of ‘Cognitive COVID.’ Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic’s unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.

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Influence of Post-Injection Parameters on Soot Formation and Oxidation in a Common-Rail-Diesel Engine Using Multi-Color-Pyrometry

ASME 2012 Internal Combustion Engine Division Fall Technical Conference ◽

10.1115/icef2012-92075 ◽

2012 ◽

Cited By ~ 15

Author(s):

Christophe Barro ◽

Frédéric Tschanz ◽

Peter Obrecht ◽

Konstantinos Boulouchos

Keyword(s):

Oxidation Rate ◽

Time Window ◽

Soot Formation ◽

General Rule ◽

Soot Oxidation ◽

Lower Amount ◽

Post Injection ◽

Heat Addition ◽

Underlying Mechanisms ◽

A Minor

The emission trade-off between soot and NOx is an issue of major concern in automotive diesel applications. Measures need to be taken both on the engine and on the aftertreatment sides in order to optimize the engine emissions while maintaining the highest possible efficiency. It is known that post injections have a potential for exhaust soot reduction without any significant influence in the NOx emissions. However, an accurate and general rule of how to parameterize a post injection such that it provides a maximum reduction of soot emissions does not exist. Moreover, the underlying mechanisms are not understood in detail. The experimental investigation presented here provides insight into the fundamental mechanisms of soot formation and reduction due to post injections under different turbulence and reaction kinetic conditions. In parallel to the measurement of soot elementary carbon in the exhaust (using a Photo Acoustic Soot Sensor), the in-cylinder soot formation and oxidation process have been investigated with an Optical Light Probe (OLP). This sensor provides crank angle resolved information about the in-cylinder soot evolution. The experiments confirm conclusions of earlier works that soot reduction due to a post injection is mainly based on two reasons: increased turbulence (from the post injection) during soot oxidation and lower soot formation due to lower amount of fuel in the main combustion at similar load conditions. A third effect of heat addition during the soot oxidation, which was often mentioned in the literature, could not be confirmed. In addition, the experiments show that variations of turbulence (from swirl) and reaction kinetics have a minor influence on the diffusion controlled heat release rate. However, the time phasing of the soot evolution is highly influenced by these variations with only small changes in the peak soot concentration. It is shown that the soot reduction of a post injection depends on the timing. More precisely, the soot reduction capability of a post injection decreases rapidly as soon as its timing is late in the soot oxidation phase. The soot oxidation rate can only be improved by increased turbulence and heat addition from the post injection in a time window before the in-cylinder soot peak occurs. Depending on EGR and swirl level, a maximum dwell time can be defined after which the post injection effect becomes counterproductive with respect to the soot oxidation rate.

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The release of a distinct cell type from swarm colonies facilitates dissemination of Vibrio parahaemolyticus in the environment

The ISME Journal ◽

10.1038/s41396-019-0521-x ◽

2019 ◽

Vol 14 (1) ◽

pp. 230-244 ◽

Cited By ~ 7

Author(s):

Carolina Freitas ◽

Timo Glatter ◽

Simon Ringgaard

Keyword(s):

Vibrio Parahaemolyticus ◽

Cell Type ◽

Distinct Cell Type ◽

Distinct Cell

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Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats

Nutrients ◽

10.3390/nu12113225 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3225

Author(s):

Sanna Lensu ◽

Raghunath Pariyani ◽

Elina Mäkinen ◽

Baoru Yang ◽

Wisam Saleem ◽

...

Keyword(s):

Hepatic Steatosis ◽

High Fat Diet ◽

Alcoholic Fatty Liver ◽

Branched Chain Fatty Acids ◽

Hepatic Fat ◽

Branched Chain ◽

Underlying Mechanisms ◽

A Minor ◽

Alcoholic Fatty Liver Disease

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. Nuclear magnetic resonance (1H-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.

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