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Neurotransmitter Precursor

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https://www.readbyqxmd.com/read/29052089/regulation-of-neurotransmitter-release-by-amyloid-precursor-protein-through-synapsin-phosphorylation
#1
An Liu, Ying Zhang, Lifang Han, Guiqin He, Wei Xie, Zikai Zhou, Zhengping Jia
Abnormal processing of amyloid precursor protein (APP) and aggregation of the Aβ peptide are known to play a key role in the pathogenesis of Alzheimer disease, but the function of endogenous APP under normal physiological conditions remains poorly understood. In this study, we investigated presynaptic changes in APP knockout (KO) mice. We demonstrate that both sucrose-induced neurotransmission and synaptic depletion in response to high frequency stimulation are significantly enhanced in APP KO compared to wild type littermates...
October 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29031899/synapse-formation-in-the-brain-can-be-enhanced-by-co-administering-three-specific-nutrients
#2
Richard J Wurtman
The memory impairments of early Alzheimer's disease [AD] are thought to result from a deficiency in synapses within the hippocampus and related brain regions. This deficiency could result from an acceleration in synapse turnover - perhaps caused by an endogenous neurotoxin like A-beta oligomers - or from a decrease in the production of the synaptic membrane needed to form new synapses. An AD-associated decrease in synaptogenesis almost certainly does occur, inasmuch as major decreases are also observed in the numbers of hippocampal dendritic spines, the immediate cytologic precursor of glutamatergic synapses...
October 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28950161/-11-c-az10419096-a-full-antagonist-pet-radioligand-for-imaging-brain-5-ht1b-receptors
#3
Anton Lindberg, Sangram Nag, Magnus Schou, Akihiro Takano, Junya Matsumoto, Nahid Amini, Charles S Elmore, Lars Farde, Victor W Pike, Christer Halldin
INTRODUCTION: The serotonergic system is widely present in all regions of the central nervous system (CNS) and plays a key modulatory role in many of its functions. Positron emission tomography (PET) is used to study several serotonin receptors in CNS in vivo. The G-protein coupled receptor 5-HT1B is mostly present in the occipital cortex and in midbrain and is linked to several psychiatric disorders. There is evidence that agonist PET radioligands for neuroreceptors are more sensitive to endogenous neurotransmitters than antagonists...
July 21, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28950111/plasma-amino-acid-profile-in-major-depressive-disorder-analyses-in-two-independent-case-control-sample-sets
#4
Shintaro Ogawa, Norie Koga, Kotaro Hattori, Junko Matsuo, Miho Ota, Hiroaki Hori, Daimei Sasayama, Toshiya Teraishi, Ikki Ishida, Fuyuko Yoshida, Sumiko Yoshida, Takamasa Noda, Teruhiko Higuchi, Hiroshi Kunugi
Some amino acids act as neurotransmitters themselves, or are precursors of neurotransmitters. Previous studies reported inconsistent results regarding their changes in blood in major depressive disorder (MDD), which prompted us to examine plasma levels of amino acids and related molecules in two independent case-control sample sets. In total, 511 subjects were recruited. Sample set A consisted of 164 patients with MDD (147 currently depressed [dMDD]; 17 in remission, DSM-IV) and 217 healthy controls. Sample set B consisted of 65 patients (51 dMDD; 14 in remission) and 65 controls...
September 19, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28931752/l-dopa-sensitizes-vasomotor-tone-by-modulating-the-vascular-alpha1-adrenergic-receptor
#5
Daiki Masukawa, Motokazu Koga, Anna Sezaki, Yuka Nakao, Yuji Kamikubo, Tatsuo Hashimoto, Yuki Okuyama-Oki, Aderemi Caleb Aladeokin, Fumio Nakamura, Utako Yokoyama, Hiromichi Wakui, Hiroshi Ichinose, Takashi Sakurai, Satoshi Umemura, Koichi Tamura, Yoshihiro Ishikawa, Yoshio Goshima
Blood pressure is regulated by extrinsic factors including noradrenaline, the sympathetic neurotransmitter that controls cardiovascular functions through adrenergic receptors. However, the fine-tuning system of noradrenaline signaling is relatively unknown. We here show that l-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of catecholamines, sensitizes the vascular adrenergic receptor alpha1 (ADRA1) through activation of L-DOPA receptor GPR143. In WT mice, intravenous infusion of the ADRA1 agonist phenylephrine induced a transient elevation of blood pressure...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28916638/pharmacological-and-physiological-assessment-of-serotonin-formation-and-degradation-in-isolated-preparations-from-mouse-and-human-heart
#6
Ulrich Gergs, Franziska Jung, Igor B Buchwalow, Britt Hofmann, Andreas Simm, Hendrik Treede, Joachim Neumann
Using transgenic mice (TG) that overexpress the human 5-HT4a-receptor specifically in cardiomyocytes, we wanted to know whether 5-HT can be formed and degraded in the mammalian heart and whether this can likewise lead to inotropic and chronotropic effects in this TG model. We noted that the 5-HT precursor, 5-hydroxy-tryptophan (5-HTP), can exert inotropic and chronotropic effects in cardiac preparations from TG but not from wild type (WT): similar results were found in human atrial preparations, as well as in intact TG animals using echocardiography...
September 15, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28869466/heterogeneous-association-of-alzheimer-s-disease-linked-amyloid-%C3%AE-and-amyloid-%C3%AE-protein-precursor-with-synapses
#7
Katarina Willén, Agnieszka Sroka, Reisuke H Takahashi, Gunnar K Gouras
Alzheimer's disease (AD) is increasingly viewed as a disease of synapses. Loss of synapses correlates better with cognitive decline than amyloid plaques and neurofibrillary tangles, the hallmark neuropathological lesions of AD. Soluble forms of amyloid-β (Aβ) have emerged as mediators of synapse dysfunction. Aβ binds to, accumulates, and aggregates in synapses. However, the anatomical and neurotransmitter specificity of Aβ and the amyloid-β protein precursor (AβPP) in AD remain poorly understood. In addition, the relative roles of Aβ and AβPP in the development of AD, at pre- versus post-synaptic compartments and axons versus dendrites, respectively, remain unclear...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28851516/brominated-and-organophosphate-flame-retardants-target-different-neurodevelopmental-stages-characterized-with-embryonic-neural-stem-cells-and-neuronotypic-pc12-cells
#8
Theodore A Slotkin, Samantha Skavicus, Heather M Stapleton, Frederic J Seidler
In addition to their activity as endocrine disruptors, brominated and organophosphate flame retardants are suspected to be developmental neurotoxicants, although identifying their specific mechanisms for that activity has been elusive. In the current study, we evaluated the effects of several flame retardants on neurodifferentiation using two in vitro models that assess distinct "decision nodes" in neural cell development: embryonic rat neural stem cells (NSCs), which evaluate the origination of neurons and glia from precursors, and rat neuronotypic PC12 cells, which characterize a later stage where cells committed to a neuronal phenotype undergo neurite outgrowth and neurotransmitter specification...
September 1, 2017: Toxicology
https://www.readbyqxmd.com/read/28795438/a-specific-gabaergic-synapse-onto-oligodendrocyte-precursors-does-not-regulate-cortical-oligodendrogenesis
#9
Maddalena Balia, Najate Benamer, María Cecilia Angulo
In the brain, neurons establish bona fide synapses onto oligodendrocyte precursor cells (OPCs), but the function of these neuron-glia synapses remains unresolved. A leading hypothesis suggests that these synapses regulate OPC proliferation and differentiation. However, a causal link between synaptic activity and OPC cellular dynamics is still missing. In the developing somatosensory cortex, OPCs receive a major type of synapse from GABAergic interneurons that is mediated by postsynaptic γ2-containing GABAA receptors...
August 10, 2017: Glia
https://www.readbyqxmd.com/read/28794131/heterogeneous-clinical-spectrum-of-dnajc12-deficient-hyperphenylalaninemia-from-attention-deficit-to-severe-dystonia-and-intellectual-disability
#10
Francjan J van Spronsen, Nastassja Himmelreich, Véronique Rüfenacht, Nan Shen, Danique van Vliet, Mohammed Al-Owain, Khushnooda Ramzan, Salwa M Alkhalifi, Roelineke J Lunsing, Rebecca M Heiner-Fokkema, Anahita Rassi, Corinne Gemperle-Britschgi, Georg F Hoffmann, Nenad Blau, Beat Thöny
BACKGROUND: Autosomal recessive mutations in DNAJC12, encoding a cochaperone of HSP70 with hitherto unknown function, were recently described to lead to hyperphenylalaninemia, central monoamine neurotransmitter (dopamine and serotonin) deficiency, dystonia and intellectual disability in six subjects affected by homozygous variants. OBJECTIVE: Patients exhibiting hyperphenylalaninemia in whom deficiencies in hepatic phenylalanine hydroxylase and tetrahydrobiopterin cofactor metabolism had been excluded were subsequently analysed for DNAJC12 variants...
August 9, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28770114/human-app-gene-expression-alters-active-zone-distribution-and-spontaneous-neurotransmitter-release-at-the-drosophila-larval-neuromuscular-junction
#11
Ekaterina A Saburova, Alexander N Vasiliev, Violetta V Kravtsova, Elena V Ryabova, Andrey L Zefirov, Olga I Bolshakova, Svetlana V Sarantseva, Igor I Krivoi
This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28703738/abnormally-increased-secretion-in-olfactory-neuronal-precursors-from-a-case-of-schizophrenia-is-modulated-by-melatonin-a-pilot-study
#12
Montserrat G Cercós, Tania Galván-Arrieta, Marcela Valdés-Tovar, Héctor Solís-Chagoyán, Jesús Argueta, Gloria Benítez-King, Citlali Trueta
The alterations that underlie the pathophysiology of schizophrenia (SCZ) include the dysregulation of structural and functional properties of neurons. Among these, the secretion of neurotransmitters and hormones, which plays a key role for neuronal communication and development, is altered. Neuronal precursors from the human olfactory epithelium have been recently characterized as a reliable model for studying the etiopathogenesis of neuropsychiatric diseases. Our previous work has shown that melatonin enhances the development of morphological and functional features of cloned olfactory neuronal precursors (ONPs) from a healthy subject...
July 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28701930/biogenic-amines-in-insect-antennae
#13
REVIEW
Marianna I Zhukovskaya, Andrey D Polyanovsky
Insect antenna is a multisensory organ, each modality of which can be modulated by biogenic amines. Octopamine (OA) and its metabolic precursor tyramine (TA) affect activity of antennal olfactory receptor neurons. There is some evidence that dopamine (DA) modulates gustatory neurons. Serotonin can serve as a neurotransmitter in some afferent mechanosensory neurons and both as a neurotransmitter and neurohormone in efferent fibers targeted at the antennal vessel and mechanosensory organs. As a neurohormone, serotonin affects the generation of the transepithelial potential by sensillar accessory cells...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28701731/bloc-1-deficiency-causes-alterations-in-amino-acid-profile-and-in-phospholipid-and-adenosine-metabolism-in-the-postnatal-mouse-hippocampus
#14
S M van Liempd, D Cabrera, F Y Lee, E González, E C Dell'Angelica, C A Ghiani, J M Falcon-Perez
Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a protein complex involved in the formation of endosomal tubular structures that mediates the sorting of protein cargoes to specialised compartments. In this study, we present insights into the metabolic consequences caused by BLOC-1 deficiency in pallid mice, which carry a null mutation in the Bloc1s6 gene encoding an essential component of this complex. The metabolome of the hippocampus of pallid mice was analysed using an untargeted, liquid chromatography-coupled mass spectrometric approach...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697973/traffic-jam-hypothesis-relationship-between-endocytic-dysfunction-and-alzheimer-s-disease
#15
REVIEW
Nobuyuki Kimura, Katsuhiko Yanagisawa
Membrane trafficking pathways, like the endocytic pathway, carry out fundamental cellular processes that are essential for normal functioning. One such process is regulation of cell surface receptor signaling. A growing body of evidence suggests that β-amyloid protein (Aβ) plays a key role in Alzheimer's disease (AD) pathogenesis. Cleavage of Aβ from its precursor, β-amyloid precursor protein (APP), occurs through the endocytic pathway in neuronal cells. In early-stage AD, intraneuronal accumulation of abnormally enlarged endosomes is common, indicating that endosome trafficking is disrupted...
July 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28641988/wavy-multistratified-amacrine-cells-in-the-monkey-retina-contain-immunoreactive-secretoneurin
#16
Andrea S Bordt, Ye Long, Nobuo Kouyama, Elizabeth S Yamada, Jens Hannibal, David W Marshak
The goals of this study were to describe the morphology, neurotransmitter content and synaptic connections of neurons in primate retinas that contain the neuropeptide secretoneurin. Amacrine cells were labeled with antibodies to secretoneurin in macaque and baboon retinas. Their processes formed three distinct plexuses in the inner plexiform layer: one in the outermost stratum, one in the center and one in the innermost stratum. In light microscopic double immunolabeling experiments, GABA was colocalized with secretoneurin in these cells, but glycine transporter 1 and Substance P were not...
August 2017: Peptides
https://www.readbyqxmd.com/read/28638366/gonadotropin-releasing-hormone-and-its-role-in-the-enteric-nervous-system
#17
REVIEW
Bodil Ohlsson
Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone, and luteinizing hormone orchestrate the reproduction cycle and regulate the sex steroid secretion from the gonads. In mammals, GnRH1 is secreted as a hormone from the hypothalamus, whereas both GnRH1 and GnRH2 are present as neurotransmitters/peptides in various tissues, where the peptides exert many different effects. mRNA coding for GnRH1 and GnRH2 have been described in the human gastrointestinal tract, and GnRH has been found in both submucosal and myenteric neurons...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28626522/study-of-para-quinone-methide-precursors-toward-the-realkylation-of-aged-acetylcholinesterase
#18
Ryan J Yoder, Qinggeng Zhuang, Jeremy M Beck, Andrew Franjesevic, Travis G Blanton, Sydney Sillart, Tyler Secor, Leah Guerra, Jason D Brown, Carolyn Reid, Craig A McElroy, Özlem Doğan Ekici, Christopher S Callam, Christopher M Hadad
Acetylcholinesterase (AChE) is an essential enzyme that can be targeted by organophosphorus (OP) compounds, including nerve agents. Following exposure to OPs, AChE becomes phosphylated (inhibited) and undergoes a subsequent aging process where the OP-AChE adduct is dealkylated. The aged AChE is unable to hydrolyze acetylcholine, resulting in accumulation of the neurotransmitter in the central nervous system (CNS) and elsewhere. Current therapeutics are only capable of reactivating inhibited AChE. There are no known therapeutic agents to reverse the aging process or treat aged AChE...
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28624333/l-theanine-prevent-quinolinic-acid-induced-motor-deficit-and-striatal-neurotoxicity-reduction-in-oxido-nitrosative-stress-and-restoration-of-striatal-neurotransmitters-level
#19
Sumit Jamwal, Shamsher Singh, Jaskamal Singh Gill, Puneet Kumar
L-theanine has been documented to possess anti-oxidant, anti-inflammatory and neuroprotective potential in various animal models of neurological disorders. The present study was anticipated to investigate the effect of L-theanine against quinolinic acid induced motor deficits, oxido-nitrosative stress, neuro-inflammation and neurotransmitters alteration in rats. Rats were stereotaxically injected QA (200nmol/2µl saline; intrastriatal); bilaterally on 0 day and L-theanine (25 & 50mg/kg; p.o.) was administered for 21 days starting from day 1 of QA injection...
September 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28621566/glutamate-dehydrogenase-is-essential-to-sustain-neuronal-oxidative-energy-metabolism-during-stimulation
#20
Michaela C Hohnholt, Vibe H Andersen, Jens V Andersen, Sofie K Christensen, Melis Karaca, Pierre Maechler, Helle S Waagepetersen
The enzyme glutamate dehydrogenase (GDH; Glud1) catalyzes the (reversible) oxidative deamination of glutamate to α-ketoglutarate accompanied by a reduction of NAD(+) to NADH. GDH connects amino acid, carbohydrate, neurotransmitter and oxidative energy metabolism. Glutamine is a neurotransmitter precursor used by neurons to sustain the pool of glutamate, but glutamine is also vividly oxidized for support of energy metabolism. This study investigates the role of GDH in neuronal metabolism by employing the Cns- Glud1(-/-) mouse, lacking GDH in the brain (GDH KO) and metabolic mapping using (13)C-labelled glutamine and glucose...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
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