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https://www.readbyqxmd.com/read/28110217/induced-dopaminergic-neurons-a-new-promise-for-parkinson-s-disease
#1
Zhimin Xu, Xingkun Chu, Houbo Jiang, Haley Schilling, Shengdi Chen, Jian Feng
Motor symptoms that define Parkinson's disease (PD) are caused by the selective loss of nigral dopaminergic (DA) neurons. Cell replacement therapy for PD has been focused on midbrain DA neurons derived from human fetal mesencephalic tissue, human embryonic stem cells (hESC) or human induced pluripotent stem cells (iPSC). Recent development in the direct conversion of human fibroblasts to induced dopaminergic (iDA) neurons offers new opportunities for transplantation study and disease modeling in PD. The iDA neurons are generated directly from human fibroblasts in a short period of time, bypassing lengthy differentiation process from human pluripotent stem cells and the concern for potentially tumorigenic mitotic cells...
January 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28108584/astrocytic-transporters-in-alzheimer-s-disease
#2
REVIEW
Chris Ugbode, Yuhan Hu, Benjamin Whalley, Chris Peers, Marcus Rattray, Mark L Dallas
Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture...
February 1, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28108358/neurochemical-and-metabolic-effects-of-acute-and-chronic-alcohol-in-the-human-brain-studies-with-positron-emission-tomography
#3
REVIEW
Nora D Volkow, Corinde E Wiers, Ehsan Shokri-Kojori, Dardo Tomasi, Gene-Jack Wang, Ruben Baler
The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding effects, the neuroadaptations from chronic exposure that contribute to tolerance and withdrawal, and the changes in fronto-striatal circuits that lead to loss of control and enhanced motivation to drink that characterize alcohol use disorders (AUD). These include studies showing that alcohol's reinforcing effects may result not only from its enhancement of dopaminergic, GABAergic and opioid signaling but also from its caloric properties...
January 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28107783/lorcaserin-suppresses-oxycodone-self-administration-and-relapse-vulnerability-in-rats
#4
Harshini Neelakantan, Erica D Holliday, Robert G Fox, Sonja J Stutz, Sandra D Comer, Margaret Haney, Noelle C Anastasio, Frederick Gerard Moeller, Kathryn A Cunningham
Opioid use disorder (OUD) is a major public health problem. High relapse rates and poor treatment retention continue to pose major challenges in OUD treatment. Of the abused opioids, oxycodone is well described to maintain self-administration and evoke the durable conditioned responses ("cue reactivity") that result from pairing of opioid-related stimuli (e.g., paraphernalia) with repeated abuse. Serotonin (5-HT) neurotransmission, particularly through the 5-HT2C receptor (5-HT2CR), regulates psychostimulant reward and cue reactivity, and in the present experiments, we investigated the hypothesis that the selective 5-HT2CR agonist lorcaserin, which is FDA-approved for the treatment of obesity, will suppress oxycodone self-administration and oxycodone-associated cue reactivity in rats...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106159/temporal-variations-in-presynaptic-release-probability-in-the-lateral-habenula
#5
Hoyong Park, Myunghyun Cheon, Sungmin Kim, ChiHye Chung
Rhythmicity plays an important role in a number of biological systems. The habenular complex is reported to contain an intrinsic molecular clock and to show rhythmic expression of circadian clock genes and proteins including per2/PER2. In this study, we observed that there is a temporal rhythmicity in the presynaptic efficacy of the lateral habenula (LHb) neurons. We collected a substantial number of recordings at different time points of the day during the light phase. The frequency and amplitude of spontaneous excitatory transmission were increased in the afternoon compared to recordings performed in the morning...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104530/long-lasting-alterations-of-hippocampal-gabaergic-neurotransmission-in-adult-rats-following-perinatal-%C3%AE-9-thc-exposure
#6
Sarah Beggiato, Andrea Celeste Borelli, Maria Cristina Tomasini, Lucia Morgano, Tiziana Antonelli, Sergio Tanganelli, Vincenzo Cuomo, Luca Ferraro
The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored...
January 16, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28103961/a-review-of-altered-biochemistry-in-the-anterior-cingulate-cortex-of-first-episode-psychosis
#7
L Squarcina, J A Stanley, M Bellani, C A Altamura, P Brambilla
Relevant biochemicals of the brain can be quantified in vivo, non-invasively, using proton Magnetic Resonance Spectroscopy (¹H MRS). This includes metabolites associated with neural general functioning, energetics, membrane phospholipid metabolism and neurotransmission. Moreover, there is substantial evidence of implication of the frontal and prefrontal areas in the pathogenesis of psychotic disorders such as schizophrenia. In particular, the anterior cingulate cortex (ACC) plays an important role in cognitive control of emotional and non-emotional processes...
January 20, 2017: Epidemiology and Psychiatric Sciences
https://www.readbyqxmd.com/read/28101524/the-role-of-dopamine-in-anticipatory-pursuit-eye-movements-insights-from-genetic-polymorphisms-in-healthy-adults
#8
Jutta Billino, Jürgen Hennig, Karl R Gegenfurtner
There is a long history of eye movement research in patients with psychiatric diseases for which dysfunctions of neurotransmission are considered to be the major pathologic mechanism. However, neuromodulation of oculomotor control is still hardly understood. We aimed to investigate in particular the impact of dopamine on smooth pursuit eye movements. Systematic variability in dopaminergic transmission due to genetic polymorphisms in healthy subjects offers a noninvasive opportunity to determine functional associations...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28097219/key-role-of-the-dopamine-d4-receptor-in-the-modulation-of-corticostriatal-glutamatergic-neurotransmission
#9
Jordi Bonaventura, César Quiroz, Ning-Sheng Cai, Marcelo Rubinstein, Gianluigi Tanda, Sergi Ferré
Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D4 receptor with the long intracellular domain of a human DRD4 polymorphic variant associated with attention deficit hyperactivity disorder (ADHD)...
January 2017: Science Advances
https://www.readbyqxmd.com/read/28096412/transmembrane-protein-108-is-required-for-glutamatergic-transmission-in-dentate-gyrus
#10
Hui-Feng Jiao, Xiang-Dong Sun, Ryan Bates, Lei Xiong, Lei Zhang, Fang Liu, Lei Li, Hong-Sheng Zhang, Shun-Qi Wang, Ming-Tao Xiong, Mihir Patel, Alexis M Stranahan, Wen-Cheng Xiong, Bao-Ming Li, Lin Mei
Neurotransmission in dentate gyrus (DG) is critical for spatial coding, learning memory, and emotion processing. Although DG dysfunction is implicated in psychiatric disorders, including schizophrenia, underlying pathological mechanisms remain unclear. Here we report that transmembrane protein 108 (Tmem108), a novel schizophrenia susceptibility gene, is highly enriched in DG granule neurons and its expression increased at the postnatal period critical for DG development. Tmem108 is specifically expressed in the nervous system and enriched in the postsynaptic density fraction...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095073/preclinical-and-potential-applications-of-common-western-herbal-supplements-as-complementary-treatment-in-parkinson-s-disease
#11
Luke A Morgan, Oliver Grundmann
Parkinson's disease (PD) is a neurological disorder with a complex pathological etiology, which is not fully understood. Progression of PD may be the result of a buildup of iron in the substantia nigra, microglia-mediated neuroinflammation, dysfunctional mitochondria, or abnormal protein handling. Dopamine is the main neurotransmitter affected, but as the disease progresses, a decrease in all the brain's biogenic amines occurs. Current medication used in the treatment of PD aims to prevent the breakdown of dopamine or increase dopaminergic neurotransmission in the central nervous system...
January 17, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28088734/in-vivo-and-in-silico-sedative-hypnotic-like-activity-of-7-methyljuglone-isolated-from-diospyros-lotus-l
#12
Abdur Rauf, Sengul Uysal, Taibi Ben Hadda, Ghias Uddin, Muhammad Asif Nawaz, Haroon Khan, Bina S Siddiqui, Muslim Raza, Saud Bawazeer, Gokhan Zengin
Diospyros lotus L. possesses different therapeutic activities such as antioxidant, anti-proliferative, anti-microbial and sedative. However, no studies on the sedative-hypnotic activity of 7-methyljuglone are reported. In the present study, we have evaluated in vivo the anxiolytic-hypnotic like effects of 7-methyljuglone in mice with open field and phenobarbitone-induced sleeping time tests. We have also assessed in silico the involvement of GABAA, GABAB and 5HT1 neurotransmission in its mechanism of action...
January 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28088287/insulin-like-growth-factor-binding-protein-3-deficiency-leads-to-behavior-impairment-with-monoaminergic-and-synaptic-dysfunction
#13
Hongmei Dai, Yu-Ichi Goto, Masayuki Itoh
Insulin-like growth factor binding protein (IGFBP)-3 regulates IGF bioactivity, induces apoptosis, and inhibits cell growth independent of IGFs, but the functional role of IGFBP3 in the brain is not clear. In the present study, we revealed the effect of IGFBP3 on the brain by characterizing the phenotype of Igfbp3-null mice. Compared with wild-type mice, Igfbp3-null mice had significantly decreased IGF-1 content in the brain but no change in weights of brain and body. In Igfbp3-null mice, the number of dendritic spines was significantly reduced, and the dendritic diameter was thickening...
January 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28087784/interactions-between-zinc-and-allosteric-modulators-of-the-glycine-receptor
#14
Garrett L Cornelison, Anna W Daszkowski, Natasha C Pflanz, S John Mihic
The glycine receptor is a pentameric ligand-gated ion channel involved in fast inhibitory neurotransmission in the central nervous system. Zinc is an allosteric modulator of glycine receptor function, enhancing the effects of glycine at nM to low μM concentrations, and inhibiting its effects at higher concentrations. Low nM concentrations of contaminating zinc in electrophysiological buffers are capable of synergistically enhancing receptor modulation by other compounds such as ethanol. This suggests that, unless accounted for, previous studies of glycine receptor modulation were measuring the effects of modulator plus co-modulation by zinc on receptor function...
January 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28077717/complexin-mutants-reveal-partial-segregation-between-recycling-pathways-that-drive-evoked-and-spontaneous-neurotransmission
#15
Nadezhda Sabeva, Richard W Cho, Alexander Vasin, Agustin Gonzalez, J Troy Littleton, Maria Bykhovskaia
: Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077092/phylogenetic-analysis-of-ionotropic-l-glutamate-receptor-genes-in-the-bilateria-with-special-notes-on-aplysia-californica
#16
Justin B Greer, Sawsan Khuri, Lynne A Fieber
BACKGROUND: The neurotransmitter L-Glutamate (L-Glu) acting at ionotropic L-Glu receptors (iGluR) conveys fast excitatory signal transmission in the nervous systems of all animals. iGluR-dependent neurotransmission is a key component of the synaptic plasticity that underlies learning and memory. During learning, two subtypes of iGluR, α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and N-methyl-D-aspartate receptors (NMDAR), are dynamically regulated postsynaptically in vertebrates...
January 11, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28074469/development-of-cone-photoreceptors-and-their-synapses-in-the-human-and-monkey-fovea
#17
Anita Hendrickson, Chi Zhang
During retinal development, ribbon synapse assembly in the photoreceptors is a crucial step involving numerous molecules. While the developmental sequence of plexiform layers in human retina has been characterized, the molecular steps of synaptogenesis remain largely unknown. In the present study, we focused on the central rod-free region of primate retina, the fovea, to specifically investigate the development of cone photoreceptor ribbon synapses. Immunocytochemistry and electron microscopy were utilized to track the expression of photoreceptor transduction proteins and ribbon and synaptic markers in fetal human and Macaca retina...
January 11, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28073591/neuropeptide-y-neuronal-network-dysfunction-in-the-frontal-lobe-of-a-genetic-mouse-model-of-schizophrenia
#18
Shunsuke Morosawa, Shuji Iritani, Hiroshige Fujishiro, Hirotaka Sekiguchi, Youta Torii, Chikako Habuchi, Keisuke Kuroda, Kozo Kaibuchi, Norio Ozaki
Neuropeptide Y (NPY) has been found to play a critical role in various mental functions as a neurotransmitter and is involved in the development of schizophrenia, a particularly intractable psychiatric disease whose precise etiology remains unknown. Recent molecular biological investigations have identified several candidate genes which may be associated with this disease, including disrupted-in-schizophrenia 1 (DISC1). The role of DISC1 would involve neurogenesis and neuronal migration. However, the functional consequences of this gene defect have not yet been fully clarified in neuronal systems...
January 5, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28073122/central-%C3%AE-opioidergic-system-activation-evoked-by-heavy-and-severe-intensity-cycling-exercise-in-humans-a-pilot-study-using-positron-emission-tomography-with-11c-carfentanil
#19
Mikio Hiura, Muneyuki Sakata, Kenji Ishii, Jun Toyohara, Keiichi Oda, Tadashi Nariai, Kiichi Ishiwata
The central opioid receptor system likely contributes to the mechanism underlying the changes in affect elicited by exercise. Our aim was to use positron emission tomography (PET) to test whether exercise intensity influences activation of the μ-opioid receptor system in the brain, and whether changes in opioid receptor activation correlate with exercise-induced changes in affect. 7 healthy young male subjects (23±2 years) performed 20-min constant-load cycling exercises at heavy (ExH) and severe-intensity (ExS), and PET was performed using [(11)C]carfentanil as a tracer before and after each exercise...
January 2017: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/28072448/identification-of-altered-brain-metabolites-associated-with-tnap-activity-in-a-mouse-model-of-hypophosphatasia-using-untargeted-nmr-based-metabolomics-analysis
#20
Thomas Cruz, Marie Gleizes, Stéphane Balayssac, Etienne Mornet, Grégory Marsal, José Luis Millán, Myriam Malet-Martino, Lionel G Nowak, Véronique Gilard, Caroline Fonta
Tissue Nonspecific Alkaline Phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However TNAP's role in the nervous system remains poorly understood. In order to investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue...
January 10, 2017: Journal of Neurochemistry
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