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neurotransmitter deficiency

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https://www.readbyqxmd.com/read/27907065/statistical-frailty-modeling-for-quantitative-analysis-of-exocytotic-events-recorded-by-live-cell-imaging-rapid-release-of-insulin-containing-granules-is-impaired-in-human-diabetic-%C3%AE-cells
#1
Giuliana Cortese, Nikhil R Gandasi, Sebastian Barg, Morten Gram Pedersen
Hormones and neurotransmitters are released when secretory granules or synaptic vesicles fuse with the cell membrane, a process denoted exocytosis. Modern imaging techniques, in particular total internal reflection fluorescence (TIRF) microscopy, allow the investigator to monitor secretory granules at the plasma membrane before and when they undergo exocytosis. However, rigorous statistical approaches for temporal analysis of such exocytosis data are still lacking. We propose here that statistical methods from time-to-event (also known as survival) analysis are well suited for the problem...
2016: PloS One
https://www.readbyqxmd.com/read/27891231/a-pharmacokinetic-evaluation-and-metabolite-identification-of-the-ghb-receptor-antagonist-ncs-382-in-mouse-informs-novel-therapeutic-strategies-for-the-treatment-of-ghb-intoxication
#2
Garrett R Ainslie, K Michael Gibson, Kara R Vogel
Gamma-aminobutyric acid (GABA) is an endogenous inhibitory neurotransmitter and precursor of gamma-hydroxybutyric acid (GHB). NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid), a known GHB receptor antagonist, has shown significant efficacy in a murine model of succinic semialdehyde dehydrogenase deficiency (SSADHD), a heritable neurological disorder featuring chronic elevation of GHB that blocks the final step of GABA degradation. NCS-382 exposures and elimination pathways remain unknown; therefore, the goal of the present work was to obtain in vivo pharmacokinetic data in a murine model and to identify the NCS-382 metabolites formed by mouse and human...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/27873132/mechanisms-of-excessive-extracellular-glutamate-accumulation-in-temporal-lobe-epilepsy
#3
Jan Albrecht, Magdalena Zielińska
There is compelling evidence that initiation and maintenance of epileptic seizures in temporal lobe epilepsy (TLE) is facilitated by excessive accumulation in the extracellular (perisynaptic) space of the excitatory neurotransmitter glutamate (Glu). This review discusses the mechanisms underlying this phenomenon. Glu released from neurons is taken up by astrocytes and activated there by glutamine synthetase (GS) to form glutamine (Gln) which upon entry to neurons is degraded back to Glu by phosphate-activated glutaminase (PAG): this chain of reactions has been defined as the glutamine/glutamate/cycle (GGC)...
November 21, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27870896/m30-antagonizes-indoleamine-2-3-dioxygenase-activation-and-neurodegeneration-induced-by-corticosterone-in-the-hippocampus
#4
Chun-Sing Lam, George Lim Tipoe, Johnny Kong-Ching Wong, Moussa B H Youdim, Man-Lung Fung
Monoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT)...
2016: PloS One
https://www.readbyqxmd.com/read/27862146/maternal-25-hydroxyvitamin-d-is-inversely-correlated-with-fetal-serotonin
#5
Padma Murthi, Miranda Davies-Tuck, Martha Lappas, Harmeet Singh, Joanne Mockler, Rahana Rahman, Rebecca Lim, Bryan Leaw, James Doery, Euan M Wallace, Peter R Ebeling
OBJECTIVE: Maternal vitamin D deficiency during pregnancy has been linked to impaired neurocognitive development in childhood. The mechanism by which vitamin D affects childhood neurocognition is unclear but may be via interactions with serotonin, a neurotransmitter involved in fetal brain development. In this study we aimed to explore associations between maternal and fetal vitamin D concentrations, and fetal serotonin concentrations at term. STUDY DESIGN AND MEASUREMENTS: Serum 25-hydroxyitamin D (25(OH)D, nmol/L) and serotonin (5-HT, nmol/L) concentrations were measured in maternal and umbilical cord blood from mother-infant pairs (n=64)...
November 12, 2016: Clinical Endocrinology
https://www.readbyqxmd.com/read/27798097/genetic-and-pharmacological-correction-of-aberrant-dopamine-synthesis-using-patient-ipscs-with-bh4-metabolism-disorders
#6
Taizo Ishikawa, Keiko Imamura, Takayuki Kondo, Yasushi Koshiba, Satoshi Hara, Hiroshi Ichinose, Mahoko Furujo, Masako Kinoshita, Tomoko Oeda, Jun Takahashi, Ryosuke Takahashi, Haruhisa Inoue
Dopamine (DA) is a neurotransmitter in the brain, playing a central role in several disease conditions, including tetrahydrobiopterin (BH4) metabolism disorders and Parkinson's disease (PD). BH4 metabolism disorders present a variety of clinical manifestations including motor disturbance via altered DA metabolism, since BH4 is a cofactor for tyrosine hydroxylase (TH), a rate-limiting enzyme for DA synthesis. Genetically, BH4 metabolism disorders are, in an autosomal recessive pattern, caused by a variant in genes encoding enzymes for BH4 synthesis or recycling, including 6-pyruvoyltetrahydropterin synthase (PTPS) or quinonoid-dihydropteridine reductase (DHPR), respectively...
October 18, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27778340/maternal-protein-restriction-during-gestation-and-lactation-in-the-rat-results-in-increased-brain-levels-of-kynurenine-and-kynurenic-acid-in-their-adult-offspring
#7
Paula Honório de Melo Martimiano, André de Sa Braga Oliveira, Véronique Ferchaud-Roucher, Mikaël Croyal, Audrey Aguesse, Isabelle Grit, Khadija Ouguerram, Sandra Lopes de Souza, Bertrand Kaeffer, Francisco Bolaños-Jiménez
Early malnutrition is a risk factor for depression and schizophrenia. Since the offspring of malnourished dams exhibit increased brain levels of serotonin (5-HT), a tryptophan-derived neurotransmitter involved in the pathophysiology of these mental disorders, it is believed that the deleterious effects of early malnutrition on brain function are due in large part to altered serotoninergic neurotransmission resulting from impaired tryptophan (Trp) metabolism. However, tryptophan is also metabolized through the kynurenine (KYN) pathway yielding several neuroactive compounds including kynurenic (KA), Qinolinic (QA) and Xanthurenic (XA) acids...
October 25, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27776515/protective-effects-of-hydroponic-teucrium-polium-on-hippocampal-neurodegeneration-in-ovariectomized-rats
#8
K V Simonyan, V A Chavushyan
BACKGROUND: The hippocampus is a target of ovarian hormones, and is necessary for memory. Ovarian hormone loss is associated with a progressive reduction in synaptic strength and dendritic spine. Teucrium polium has beneficial effects on learning and memory. However, it remains unknown whether Teucrium polium ameliorates hippocampal cells spike activity and morphological impairments induced by estrogen deficiency. METHODS: In the present study, we investigated the effects of hydroponic Teucrium polium on hippocampal neuronal activity and morpho-histochemistry of bilateral ovariectomized (OVX) rats...
October 24, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27762066/a-new-brain-dopamine-deficient-drosophila-and-its-pharmacological-and-genetic-rescue
#9
Karol Cichewicz, Emma J Garren, Chika Adiele, Yoshinori Aso, Zhang Wang, Martin Wu, Serge Birman, Gerald M Rubin, Jay Hirsh
Dopamine (DA) is a neurotransmitter with conserved behavioral roles between invertebrate and vertebrate animals. In addition to its neural functions, in insects DA is a critical substrate for cuticle pigmentation and hardening. Drosophila tyrosine hydroxylase (DTH) is the rate limiting enzyme for DA biosynthesis. Viable brain DA deficient flies were previously generated using tissue selective GAL4-UAS binary expression rescue of a DTH null mutation and these flies show specific behavioral impairments. To circumvent the limitations of rescue via binary expression, here we achieve rescue utilizing genomically integrated mutant DTH...
October 19, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27760889/g-aminobutyric-acid-promotes-methionine-choline-deficient-diet-induced-nonalcoholic-steatohepatitis
#10
Seok Roh Yoon, Cho Ara, Zhou Zixiong, Jeong Hyuneui, Park Jeong-Eun, Cha Youn-Soo, Oh Suk-Heung, Lim Chae-Woong, Kim Bumseok
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects...
October 17, 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27734716/a-review-of-the-role-of-synaptosomal-associated-protein-25-snap-25-in-neurological-disorders
#11
Aneeqa Noor, Saadia Zahid
Synaptosomal-associated protein 25 kDa (SNAP-25) is one of the key proteins involved in formation of neural soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, which are responsible for the calcium-dependent exocytosis of neurotransmitters - a major step in neurotransmission and the key to normal functioning of brain. Several studies have reported abnormalities in its expression and structure and highlighted it as an important player in pathology of various neurological disorders like Alzheimer's disease, schizophrenia, attention deficient hyperactivity disorder, epilepsy and few others...
October 13, 2016: International Journal of Neuroscience
https://www.readbyqxmd.com/read/27690368/hereditary-dopamine-transporter-deficiency-syndrome-challenges-in-diagnosis-and-treatment
#12
Yilmaz Yildiz, Emine Pektas, Aysegul Tokatli, Goknur Haliloglu
Hereditary dopamine transporter deficiency syndrome (DTDS) is a neurotransmitter disorder caused by a defect in the neuronal uptake of dopamine. To date, 20 patients are reported in the literature, and we present 2 additional patients with DTDS harboring novel homozygous SLC6A3 gene mutations. Patient A is an 8-month-old male with neonatal-onset hypotonia, who developed orolingual dyskinetic movements and oculogyric crises after 4 months of age, with evolution to status dystonicus episodes. Patient B is a 4-year-old male who also had hypotonia since birth, with additional severe limb contractions and oculogyric crises after the age of 3 months, with a misdiagnosis of epileptic encephalopathy...
September 30, 2016: Neuropediatrics
https://www.readbyqxmd.com/read/27677260/gnb5-mutation-causes-a-novel-neuropsychiatric-disorder-featuring-attention-deficit-hyperactivity-disorder-severely-impaired-language-development-and-normal-cognition
#13
Hanan E Shamseldin, Ikuo Masuho, Ahmed Alenizi, Suad Alyamani, Dipak N Patil, Niema Ibrahim, Kirill A Martemyanov, Fowzan S Alkuraya
BACKGROUND: Neuropsychiatric disorders are common forms of disability in humans. Despite recent progress in deciphering the genetics of these disorders, their phenotypic complexity continues to be a major challenge. Mendelian neuropsychiatric disorders are rare but their study has the potential to unravel novel mechanisms that are relevant to their complex counterparts. RESULTS: In an extended consanguineous family, we identified a novel neuropsychiatric phenotype characterized by severe speech impairment, variable expressivity of attention deficit hyperactivity disorder (ADHD), and motor delay...
September 27, 2016: Genome Biology
https://www.readbyqxmd.com/read/27671655/rim-binding-protein-2-regulates-release-probability-by-fine-tuning-calcium-channel-localization-at-murine-hippocampal-synapses
#14
M Katharina Grauel, Marta Maglione, Suneel Reddy-Alla, Claudia G Willmes, Marisa M Brockmann, Thorsten Trimbuch, Tanja Rosenmund, Maria Pangalos, Gülçin Vardar, Alexander Stumpf, Alexander M Walter, Benjamin R Rost, Britta J Eickholt, Volker Haucke, Dietmar Schmitz, Stephan J Sigrist, Christian Rosenmund
The tight spatial coupling of synaptic vesicles and voltage-gated Ca(2+) channels (CaVs) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM-BPs) interact with Ca(2+) channels and via RIM with other components of the release machinery. Although human RIM-BPs have been implicated in autism spectrum disorders, little is known about the role of mammalian RIM-BPs in synaptic transmission. We investigated RIM-BP2-deficient murine hippocampal neurons in cultures and slices...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27666382/suboptimal-maternal-diets-alter-mu-opioid-receptor-and-dopamine-type-1-receptor-binding-but-exert-no-effect-on-dopamine-transporters-in-the-offspring-brain
#15
Panayotis K Thanos, Jianmin Zhuo, Lisa Robison, Ronald Kim, Mala Ananth, Ilon Choai, Adam Grunseich, Nicola M Grissom, Robert George, Foteini Delis, Teresa M Reyes
Birthweight is a marker for suboptimal fetal growth and development in utero. Offspring can be born large for gestational age (LGA), which is linked to maternal obesity or excessive gestational weight gain, as well as small for gestational age (SGA), arising from nutrient or calorie deficiency, placental dysfunction, or other maternal conditions (hypertension, infection). In humans, LGA and SGA babies are at an increased risk for certain neurodevelopmental disorders, including Attention Deficit/Hyperactivity Disorder, schizophrenia, and social and mood disorders...
September 22, 2016: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/27658936/mutation-adapted-u1-snrna-corrects-a-splicing-error-of-the-dopa-decarboxylase-gene
#16
Ni-Chung Lee, Yu-May Lee, Pin-Wen Chen, Barry J Byrne, Wuh-Liang Hwu
Aromatic L-amino acid decarboxylase (AADC) deficiency is an inborn error of monoamine neurotransmitter synthesis, which results in dopamine, serotonin, epinephrine, and norepinephrine deficiencies. The DDC gene founder mutation IVS6+4A>T is highly prevalent in Chinese patients with AADC deficiency. In this study, we designed several U1 snRNA vectors to adapt U1 snRNA binding sequences of the mutated DDC gene. We found that only the modified U1 snRNA (IVS-AAA) that completely matched both the intronic and exonic U1 binding sequences of the mutated DDC gene could correct splicing errors of either the mutated human DDC minigene or the mouse artificial splicing construct in vitro We further injected an adeno-associated viral (AAV) vector to express IVS-AAA in the brain of a knock-in mouse model...
September 21, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27644916/-iron-deficiency-a-diagnostic-and-therapeutic-perspective-in-psychiatry
#17
A Kassir
BACKGROUND: Iron plays an essential role in balancing the various metabolism in the body. It is also involved in the synthesis of several neurotransmitters. Nutritional iron deficiency is one of the most widespread worldwide; it poses a great health challenge due to the consequences it entails. OBJECTIVES: The aim of this research study is to explore the percentage of psychiatric patients who have a deficiency in iron. In addition, the study investigates the efficacy of iron administered by oral treatment on psychiatric symptomatology among iron deficient patients...
September 16, 2016: L'Encéphale
https://www.readbyqxmd.com/read/27639349/subconvulsant-doses-of-pentylenetetrazol-uncover-the-epileptic-phenotype-of-cultured-synapsin-deficient-helix-serotonergic-neurons-in-the-absence-of-excitatory-and-inhibitory-inputs
#18
Oscar Brenes, Valentina Carabelli, Sara Gosso, Adarli Romero, Emilio Carbone, Pier Giorgio Montarolo, Mirella Ghirardi
Synapsins are a family of presynaptic proteins related to several processes of synaptic functioning. A variety of reports have linked mutations in synapsin genes with the development of epilepsy. Among the proposed mechanisms, a main one is based on the synapsin-mediated imbalance towards network hyperexcitability due to differential effects on neurotransmitter release in GABAergic and glutamatergic synapses. Along this line, a non-synaptic effect of synapsin depletion increasing neuronal excitability has recently been described in Helix neurons...
September 6, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27638595/metabolic-profiling-reveals-biochemical-pathways-and-potential-biomarkers-associated-with-the-pathogenesis-of-krabbe-disease
#19
Nadav I Weinstock, Lawrence Wrabetz, M Laura Feltri, Daesung Shin
Krabbe disease (KD) is caused by mutations in the galactosylceramidase (GALC) gene, which encodes a lysosomal enzyme that degrades galactolipids, including galactosylceramide and galactosylsphingosine (psychosine). GALC deficiency results in progressive intracellular accumulation of psychosine, which is believed to be the main cause for the demyelinating neurodegeneration in KD pathology. Umbilical cord blood transplantation slows disease progression when performed presymptomatically but carries a significant risk of morbidity and mortality...
November 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27616302/sex-and-intrauterine-growth-restriction-modify-brain-neurotransmitters-profile-of-newborn-piglets
#20
M Vázquez-Gómez, D Valent, C García-Contreras, L Arroyo, C Óvilo, B Isabel, A Bassols, A González-Bulnes
The current study aimed to determine, using a swine model of intrauterine growth restriction (IUGR), whether short- and long-term neurological deficiencies and interactive dysfunctions of Low Birth-Weight (LBW) offspring might be related to altered pattern of neurotransmitters. Hence, we compared the quantities of different neurotransmitters (catecholamines and indoleamines), which were determined by HPLC, at brain structures related to the limbic system (hippocampus and amygdala) in 14 LBW and 10 Normal Body-Weight (NBW) newborn piglets...
September 9, 2016: International Journal of Developmental Neuroscience
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