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https://www.readbyqxmd.com/read/29212780/excitatory-gabaergic-action-and-increased-vasopressin-synthesis-in-hypothalamic-magnocellular-neurosecretory-cells-underlie-the-high-plasma-level-of-vasopressin-in-diabetic-rat
#1
Young-Beom Kim, Woong Bin Kim, Won Woo Jung, Xiangyan Jin, Yoon Sik Kim, Byoungjae Kim, Hee Chul Han, Gene D Block, Christopher S Colwell, Yang In Kim
Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP) which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in the supraoptic nucleus (SON) slices from streptozotocin-induced DM model (STZ) rats and vehicle-treated control rats revealed that GABA functions generally as an excitatory neurotransmitter in the AVP neurons of STZ rats, whereas it evoked usually inhibitory responses in the cells of control animals...
December 6, 2017: Diabetes
https://www.readbyqxmd.com/read/29209914/a-mathematical-model-supports-a-key-role-for-ae4-slc4a9-in-salivary-gland-secretion
#2
Elías Vera-Sigüenza, Marcelo A Catalán, Gaspar Peña-Münzenmayer, James E Melvin, James Sneyd
We develop a mathematical model of a salivary gland acinar cell with the objective of investigating the role of two [Formula: see text] exchangers from the solute carrier family 4 (Slc4), Ae2 (Slc4a2) and Ae4 (Slc4a9), in fluid secretion. Water transport in this type of cell is predominantly driven by [Formula: see text] movement. Here, a basolateral [Formula: see text] adenosine triphosphatase pump (NaK-ATPase) and a [Formula: see text]-[Formula: see text]-[Formula: see text] cotransporter (Nkcc1) are primarily responsible for concentrating the intracellular space with [Formula: see text] well above its equilibrium potential...
December 5, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29209227/the-role-of-na-k-2cl-cotransporter-1-nkcc1-slc12a2-in-dental-epithelium-during-enamel-formation-in-mice
#3
Rozita Jalali, Johannes C Lodder, Behrouz Zandieh-Doulabi, Dimitra Micha, James E Melvin, Marcelo A Catalan, Huibert D Mansvelder, Pamela DenBesten, Antonius Bronckers
Na+:K+:2Cl- cotransporters (NKCCs) belong to the SLC12A family of cation-coupled Cl- transporters. We investigated whether enamel-producing mouse ameloblasts express NKCCs. Transcripts for Nkcc1 were identified in the mouse dental epithelium by RT-qPCR and NKCC1 protein was immunolocalized in outer enamel epithelium and in the papillary layer but not the ameloblast layer. In incisors of Nkcc1-null mice late maturation ameloblasts were disorganized, shorter and the mineral density of the enamel was reduced by 10% compared to wild-type controls...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29197149/cd29-is-highly-expressed-on-epithelial-myoepithelial-and-mesenchymal-stromal-cells-of-human-salivary-glands
#4
Padma Priya Togarrati, Nuntana Dinglasan, Shivani Desai, William R Ryan, Marcus O Muench
OBJECTIVE: The phenotype of the cells present in the ductal region of salivary glands have been well characterized. However, it is imperative to identify novel biomarkers that can identify different cell types present in other glandular components for the development of therapeutic strategies and diagnostics of salivary gland disorders and malignancies. Our study aimed at the characterization of the expression and distribution of various cell surface markers, especially with a focus on CD29 in human fetal as well as adult glands...
December 2, 2017: Oral Diseases
https://www.readbyqxmd.com/read/29160910/epithelial-disruptions-but-not-immune-cell-invasion-induced-secretory-dysfunction-following-innate-immune-activation-in-a-novel-model-of-acute-salivary-gland-injury
#5
Abeer Shaalan, Guy Carpenter, Gordon Proctor
BACKGROUND: Salivary gland (SG) injurious agents are all translated into loss of salivation (xerostomia). An association has been established between activation of innate immunity and salivary gland injury and dysfunction. However, it remains unclear how the secretory epithelia respond by halting saliva production. METHODS: C57BL/6 submandibular glands (SMGs) were acutely challenged using a single dose of the innate immune stimulant: polyinosinic-polycytidylic acid (poly (I:C))...
November 21, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29146941/developmental-excitatory-to-inhibitory-gaba-polarity-switch-is-disrupted-in-22q11-2-deletion-syndrome-a-potential-target-for-clinical-therapeutics
#6
Hayder Amin, Federica Marinaro, Davide De Pietri Tonelli, Luca Berdondini
Individuals with 22q11.2 microdeletion syndrome (22q11.2 DS) show cognitive and behavioral dysfunctions, developmental delays in childhood and risk of developing schizophrenia and autism. Despite extensive previous studies in adult animal models, a possible embryonic root of this syndrome has not been determined. Here, in neurons from a 22q11.2 DS mouse model (Lgdel (+/-)), we found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051615/time-controllable-nkcc1-knockdown-replicates-reversible-hearing-loss-in-postnatal-mice
#7
Takahisa Watabe, Ming Xu, Miho Watanabe, Junichi Nabekura, Taiga Higuchi, Karin Hori, Mitsuo P Sato, Fumiaki Nin, Hiroshi Hibino, Kaoru Ogawa, Masatsugu Masuda, Kenji F Tanaka
Identification of the causal effects of specific proteins on recurrent and partially reversible hearing loss has been difficult because of the lack of an animal model that provides reversible gene knockdown. We have developed the transgenic mouse line Actin-tTS::Nkcc1 (tetO/tetO) for manipulatable expression of the cochlear K(+) circulation protein, NKCC1. Nkcc1 transcription was blocked by the binding of a tetracycline-dependent transcriptional silencer to the tetracycline operator sequences inserted upstream of the Nkcc1 translation initiation site...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29035834/synergistic-effect-of-mild-hypothermia-and-the-notch-inhibitor-dapt-against-post-stroke-seizures
#8
Guo-Shuai Yang, Xiao-Yan Zhou, Xue-Fang An, Xuan-Jun Liu, Yan-Jun Zhang, Dan Yu
Seizure is a serious complication of stroke, indicating poor prognosis. Notch signaling is associated with neuronal activity. Inhibition of Notch signaling suppresses seizure activity induced by kainic acid. The present study investigated the effect of the Notch inhibitor, DAPT, alone or in combination with mild hypothermia, on post-stroke seizures. A global cerebral ischemia (GCI) model was performed in Sprague Dawley (SD) male rats. Seizure activity was evaluated by the frequency of seizure attacks, seizure severity scores, and seizure discharges...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29029515/discovery-of-nkcc1-as-a-potential-therapeutic-target-to-inhibit-hepatocellular-carcinoma-cell-growth-and-metastasis
#9
Yaya Zhou, Wei Sun, Ning Chen, Chen Xu, Xinxin Wang, Kun Dong, Binxue Zhang, Jian Zhang, Ning Hao, Aihua Sun, Handong Wei, Fuchu He, Ying Jiang
Metastasis is the essential cause for the high mortality of hepatocellular carcinoma (HCC). In order to investigate the mechanism of metastasis, and to discover therapeutic targets for HCC, the quantitative proteomic technique was applied to characterize the plasma membrane proteins of two HCC cell lines with low (MHCC97L) or high (MHCC97H) metastatic potentials. One of the plasma membrane proteins, sodium-potassium-chloride cotransporter 1 (NKCC1), was upregulated in MHCC97H cell line. Immunohistochemistry result in HCC patients showed that NKCC1 expression was associated with poor differentiation and microvascular invasion...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28994331/evaluating-the-involvement-of-cerebral-microvascular-endothelial-na-k-atpase-and-na-k-2cl-co-transporter-in-electrolyte-fluxes-in-an-in%C3%A2-vitro-blood-brain-barrier-model-of-dehydration
#10
Kasper Lykke, Mette Assentoft, Sofie Hørlyck, Hans Cc Helms, Anca Stoica, Trine L Toft-Bertelsen, Katerina Tritsaris, Frederik Vilhardt, Birger Brodin, Nanna MacAulay
The blood-brain barrier (BBB) is involved in brain water and salt homeostasis. Blood osmolarity increases during dehydration and water is osmotically extracted from the brain. The loss of water is less than expected from pure osmotic forces, due to brain electrolyte accumulation. Although the underlying molecular mechanisms are unresolved, the current model suggests the luminally expressed Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) as a key component, while the role of the Na(+)/K(+)-ATPase remains uninvestigated...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28982596/subsequent-maternal-separation-exacerbates-neurobehavioral-abnormalities-in-rats-neonatally-exposed-to-sevoflurane-anesthesia
#11
Jiaojiao Yang, Lingsha Ju, Min Jia, Hui Zhang, Xiaoru Sun, Muhuo Ji, Jianjun Yang, Anatoly E Martynyuk
Several recent studies suggest that in the human population, a routine, short anesthetic in otherwise healthy infants is void of neurodevelopmental insult. On the other hand, many human retrospective epidemiological studies report evidence of cognitive abnormalities in children after testing those who had different anesthesia-requiring procedures in early childhood. We tested in a rat model whether post-anesthesia stressful environmental factors can contribute to developmental abnormalities that were initiated by a relatively short exposure to sevoflurane, the most widely used anesthetic in pediatric anesthesia, whose polyvalent actions include enhancement of gamma-aminobutyric acid type A receptor (GABAAR) activity...
November 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28964752/inhibition-of-nkcc1-promotes-axonal-growth-and-motor-recovery-in-ischemic-rats
#12
X P Mu, H B Wang, X Cheng, L Yang, X Y Sun, H L Qu, S S Zhao, Z K Zhou, T T Liu, T Xiao, B Song, J Jolkkonen, C S Zhao
Bumetanide is a selective inhibitor of the Na(+)-K(+)-Cl(-)-co-transporter 1(NKCC1). We studied whether bumetanide could affect axonal growth and behavioral outcome in stroke rats. Adult male Wistar rats were randomly assigned to four groups: sham-operated rats treated with vehicle or bumetanide, and ischemic rats treated with vehicle or bumetanide. Endothelin-1 was used to induce focal cerebral ischemia. Bumetanide administration (i.c.v.) started on postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine (BDA) was injected into the right imotor cortex on postoperative day 14 to trace corticospinal tract (CST) fibers sprouting into the denervated cervical spinal cord...
December 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28928398/bumetanide-treatment-during-early-development-rescues-maternal-separation-induced-susceptibility-to-stress
#13
Die Hu, Zhou-Long Yu, Yan Zhang, Ying Han, Wen Zhang, Lin Lu, Jie Shi
Stress is a major risk factor for psychiatric disorders, such as depression, posttraumatic stress disorder, and schizophrenia. Early life stress, such as maternal separation, can have long-term effects on the development of the central nervous system and pathogenesis of psychiatric disorders. In the present study, we found that maternal separation increased the susceptibility to stress in adolescent rats, increased the expression of Na(+)/K(+)/2Cl(-) cotransporter 1 (NKCC1) on postnatal day 14, and increased the expression of K(+)/2Cl(-) cotransporter 2 (KCC2) and γ-aminobutyric acid A (GABAA) receptor subunits on postnatal day 40 in the hippocampus...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860458/intracellular-chloride-regulation-in-avp-and-vip-neurons-of-the-suprachiasmatic-nucleus
#14
Nathan J Klett, Charles N Allen
Several reports have described excitatory GABA transmission in the suprachiasmatic nucleus (SCN), the master pacemaker of circadian physiology. However, there is disagreement regarding the prevalence, timing, and neuronal location of excitatory GABA transmission in the SCN. Whether GABA is inhibitory or excitatory depends, in part, on the intracellular concentration of chloride ([Cl(-)]i). Here, using ratiometric Cl(-) imaging, we have investigated intracellular chloride regulation in AVP and VIP-expressing SCN neurons and found evidence suggesting that [Cl(-)]i is higher during the day than during the night in both AVP+ and VIP+ neurons...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818393/the-modulation-of-the-phosphorylation-status-of-nkcc1-in-organ-cultured-bovine-lenses-implications-for-the-regulation-of-fiber-cell-and-overall-lens-volume
#15
Irene Vorontsova, Paul J Donaldson, Zhiying Kong, Chiharu Wickremesinghe, Leo Lam, Julie C Lim
In previous work, we have shown the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to be a key effector of lens fiber cell volume regulation. Since others have shown that the activity of NKCC1 is regulated via its phosphorylation status, the purpose of this study was to investigate whether NKCC1 phosphorylation can be modulated in organ cultured bovine lenses, and to see how this relates to changes in lens wet weight. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level...
August 14, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28818303/nkcc1-chloride-importer-antagonists-attenuate-many-neurological-and-psychiatric-disorders
#16
REVIEW
Yehezkel Ben-Ari
In physiological conditions, adult neurons have low intracellular Cl(-) [(Cl(-))I] levels underlying the γ-aminobutyric acid (GABA)ergic inhibitory drive. In contrast, neurons have high (Cl(-))I levels and excitatory GABA actions in a wide range of pathological conditions including spinal cord lesions, chronic pain, brain trauma, cerebrovascular infarcts, autism, Rett and Down syndrome, various types of epilepsies, and other genetic or environmental insults. The diuretic highly specific NKCC1 chloride importer antagonist bumetanide (PubChem CID: 2461) efficiently restores low (Cl(-))I levels and attenuates many disorders in experimental conditions and in some clinical trials...
September 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28801579/tnf%C3%AE-induced-up-regulation-of-na-k-2cl-cotransporter-nkcc1-in-hepatic-ammonia-clearance-and-cerebral-ammonia-toxicity
#17
Vitaly I Pozdeev, Elisabeth Lang, Boris Görg, Hans J Bidmon, Prashant V Shinde, Gerald Kircheis, Diran Herebian, Klaus Pfeffer, Florian Lang, Dieter Häussinger, Karl S Lang, Philipp A Lang
The devastating consequences of hepatic failure include hepatic encephalopathy, a severe, life threatening impairment of neuronal function. Hepatic encephalopathy is caused by impaired hepatic clearance of NH4(+). Cellular NH4(+) uptake is accomplished mainly by the Na(+),K(+),2Cl(-) cotransporter. Here we show that hepatic clearance of NH4(+) is impaired in TNFα deficient as well as TNFR1&TNFR2 double knockout mice, which both develop hyperammonemia. Despite impaired hepatic clearance of NH4(+), TNFα deficient mice and TNFR1 deficient mice were protected against acute ammonia intoxication...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796813/a-novel-organotypic-3d-sweat-gland-model-with-physiological-functionality
#18
Patricia Klaka, Sabine Grüdl, Bernhard Banowski, Melanie Giesen, Andrea Sättler, Peter Proksch, Thomas Welss, Thomas Förster
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers...
2017: PloS One
https://www.readbyqxmd.com/read/28692063/inflammation-dependent-cerebrospinal-fluid-hypersecretion-by-the-choroid-plexus-epithelium-in-posthemorrhagic-hydrocephalus
#19
Jason K Karimy, Jinwei Zhang, David B Kurland, Brianna Carusillo Theriault, Daniel Duran, Jesse A Stokum, Charuta Gavankar Furey, Xu Zhou, M Shahid Mansuri, Julio Montejo, Alberto Vera, Michael L DiLuna, Eric Delpire, Seth L Alper, Murat Gunel, Volodymyr Gerzanich, Ruslan Medzhitov, J Marc Simard, Kristopher T Kahle
The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept...
August 2017: Nature Medicine
https://www.readbyqxmd.com/read/28679951/a-salt-sensing-kinase-in-t-lymphocytes-sgk1-drives-hypertension-and-hypertensive-end-organ-damage
#20
Allison E Norlander, Mohamed A Saleh, Arvind K Pandey, Hana A Itani, Jing Wu, Liang Xiao, Jooeun Kang, Bethany L Dale, Slavina B Goleva, Fanny Laroumanie, Liping Du, David G Harrison, Meena S Madhur
We previously showed that angiotensin II (Ang II) increases T cell production of IL-17A, and that mice deficient in IL-17A have blunted hypertension and attenuated renal and vascular dysfunction. It was recently shown that salt enhances IL-17A production from CD4+ T cells via a serum- and glucocorticoid-regulated kinase 1-dependent (SGK1-dependent) pathway. Thus, we tested the hypothesis that SGK1 signaling in T cells promotes hypertension and contributes to end-organ damage. We show that loss of T cell SGK1 results in a blunted hypertensive response to Ang II infusion by 25 mmHg...
July 6, 2017: JCI Insight
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