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https://www.readbyqxmd.com/read/29336676/vasopressors-in-sepsis
#1
Kristin P Colling, Kaysie L Banton, Greg J Beilman
BACKGROUND: Sepsis accounts for 10% of intensive care unit admissions and significant healthcare costs. Although the mortality rate from sepsis has been decreasing with better critical care, early identification of septic patients, and prompt interventions, the mortality rate remains 20%-30%. METHOD: Review of the English-language literature. RESULTS: Norepinephrine is the first-line vasopressor in shock and is associated with a lower mortality rate as well as fewer adverse effects...
January 16, 2018: Surgical Infections
https://www.readbyqxmd.com/read/29335072/rebound-excitability-mediates-motor-abnormalities-in-parkinson-s-disease
#2
Jeongjin Kim, Daesoo Kim
Parkinson's disease (PD) is a debilitating disorder resulting from loss of dopamine neurons. In dopamine deficient state, the basal ganglia increases inhibitory synaptic outputs to the thalamus. This increased inhibition by the basal ganglia output is known to reduce firing rate of thalamic neurons that relay motor signals to the motor cortex. This 'rate model' suggests that the reduced excitability of thalamic neurons is the key for inducing motor abnormalities in PD patients. We reveal that in response to inhibition, thalamic neurons generate rebound firing at the end of inhibition...
January 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29331172/blood-phenylalanine-reduction-corrects-cns-dopamine-and-serotonin-deficiencies-and-partially-improves-behavioral-performance-in-adult-phenylketonuric-mice
#3
Shelley R Winn, Tanja Scherer, Beat Thöny, Ming Ying, Aurora Martinez, Sydney Weber, Jacob Raber, Cary O Harding
Central nervous system (CNS) deficiencies of the monoamine neurotransmitters dopamine and serotonin have been implicated in the pathophysiology of neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we confirmed the occurrence of brain dopamine and serotonin deficiencies in association with severe behavioral alterations and cognitive impairments in hyperphenylalaninemic C57BL/6-Pahenu2/enu2 mice, a model of human PKU. Phenylalanine-reducing treatments, including either dietary phenylalanine restriction or liver-directed gene therapy, initiated during adulthood were associated with increased brain monoamine content along with improvements in nesting behavior but without a change in the severe cognitive deficits exhibited by these mice...
January 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29321592/amyloid-%C3%AE-causes-excitation-inhibition-imbalance-through-dopamine-receptor-1-dependent-disruption-of-fast-spiking-gabaergic-input-in-anterior-cingulate-cortex
#4
Si-Qiang Ren, Wen Yao, Jing-Zhi Yan, Chunhui Jin, Jia-Jun Yin, Jianmin Yuan, Shui Yu, Zaohuo Cheng
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. At the early stages of AD development, the soluble β-amyloid (Aβ) induces synaptic dysfunction, perturbs the excitation/inhibition balance of neural circuitries, and in turn alters the normal neural network activity leading to cognitive decline, but the underlying mechanisms are not well established. Here by using whole-cell recordings in acute mouse brain slices, we found that 50 nM Aβ induces hyperexcitability of excitatory pyramidal cells in the cingulate cortex, one of the most vulnerable areas in AD, via depressing inhibitory synaptic transmission...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318783/tak-063-a-novel-pde10a-inhibitor-with-balanced-activation-of-direct-and-indirect-pathways-provides-a-unique-opportunity-for-the-treatment-of-schizophrenia
#5
REVIEW
Kazunori Suzuki, Haruhide Kimura
The basal ganglia regulates motor, cognitive, and emotional behaviors. Dysfunction of dopamine system in this area is implicated in the pathophysiology of schizophrenia characterized by positive symptoms, negative symptoms, and cognitive deficits. Medium spiny neurons (MSNs) are principal output neurons of striatum in the basal ganglia. Similar to current antipsychotics with dopamine D2 receptor antagonism or partial agonism, phosphodiesterase 10A (PDE10A) inhibitors activate indirect pathway MSNs, leading to the expectation of therapeutic potential for the treatment of psychosis...
January 9, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29311685/synaptotagmin-11-is-a-critical-mediator-of-parkin-linked-neurotoxicity-and-parkinson-s-disease-like-pathology
#6
Changhe Wang, Xinjiang Kang, Li Zhou, Zuying Chai, Qihui Wu, Rong Huang, Huadong Xu, Meiqin Hu, Xiaoxuan Sun, Suhua Sun, Jie Li, Ruiying Jiao, Panli Zuo, Lianghong Zheng, Zhenyu Yue, Zhuan Zhou
Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiological substrate of parkin and plays critical roles in mediating parkin-linked neurotoxicity. Unilateral overexpression of full-length, but not C2B-truncated, synaptotagmin-11 in the substantia nigra pars compacta (SNpc) impairs ipsilateral striatal dopamine release, causes late-onset degeneration of dopaminergic neurons, and induces progressive contralateral motor abnormalities...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29301039/defining-the-locus-of-dopaminergic-dysfunction-in-schizophrenia-a-meta-analysis-and-test-of-the-mesolimbic-hypothesis
#7
Robert McCutcheon, Katherine Beck, Sameer Jauhar, Oliver D Howes
Background: Studies using positron emission tomography to image striatal dopamine function, have demonstrated that individuals with schizophrenia display increases in presynaptic function. Mesolimbic dysfunction specifically, has previously been suggested to underlie psychotic symptoms. This has not been directly tested in vivo, and the precise anatomical locus of dopamine dysfunction within the striatum remains unclear. The current article investigates the magnitude of dopaminergic abnormalities in individuals with schizophrenia, and determines how the magnitude of abnormality varies across functional subdivisions of the striatum...
December 28, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29299922/stabilization-of-human-tyrosine-hydroxylase-in-maltodextrin-nanoparticles-for-delivery-to-neuronal-cells-and-tissue
#8
Maria Teresa Bezem, Fredrik Gullaksen Johannessen, Kunwar Jung-Kc, Edvin Tang Gundersen, Ana Jorge-Finnigan, Ming Ying, Didier Betbeder, Lars Herfindal, Aurora Martinez
Enzyme replacement therapy (ERT) is a therapeutic approach envisioned decades ago for the correction of genetic disorders, but it is only after improvements in recombinant protein expression and purification that the applicability of this approach has increased. Customarily, ERT has been less successful for the correction of disorders with neurological manifestations. In this work we have tested the functionality of nanoparticles (NP) composed of maltodextrin with a lipid core to bind and stabilize tyrosine hydroxylase (TH), which is a complex and unstable brain enzyme that catalyzes the rate limiting step in the synthesis of dopamine and other catecholamine neurotransmitters...
January 4, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29298719/association-between-cerebral-dopamine-neurotrophic-factor-cdnf-2-polymorphisms-and-schizophrenia-susceptibility-and-symptoms-in-the-han-chinese-population
#9
Yongfeng Yang, Hongyan Yu, Wenqiang Li, Bing Liu, Hongxing Zhang, Shuang Ding, Yanli Lu, Tianzi Jiang, Luxian Lv
BACKGROUND: Schizophrenia (SZ) is a complex polygenic psychiatric disorder caused in part by abnormal dopamine levels. Cerebral dopamine neurotrophic factor (CDNF) 2 is known to protect and repair the dopaminergic system. Dopamine dysfunction is one of the pathogenesis of SZ. However, the relationship between CDNF2 and SZ has not been previously investigated. We speculated that CDNF2 may be a susceptibility factor for SZ. METHODS: To address this issue, we carried out a study to investigate the association between CDNF2 and SZ in the total sample 1371 (670 SZ patients and 701 healthy controls) Han Chinese population...
January 3, 2018: Behavioral and Brain Functions: BBF
https://www.readbyqxmd.com/read/29282341/-tourette-syndrome-clinical-features-and-pathophysiology
#10
Yoshiko Nomura
Tourette syndrome (TS) is a neuropsychiatric disorder with the onset in childhood. TS is a form of tic disorders, and characterized by the motor and vocal tics, and comorbidities such as attention deficit hyperkinetic and obsessive compulsive disorders. These symptoms appear age dependently, showing a wax and wane course, and subside or abolish by the late teens. Pathophysiology of TS involves the dysfunction of both motor and non-motor basal ganglia-thalamo-cortical circuitries. The nigrostriatal dopamine (DA) system takes the exponential decrement at the striatum...
December 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29277488/ghrelin-mediated-neuroprotection-a-possible-therapy-for-parkinson-s-disease
#11
REVIEW
Alwena H Morgan, Daniel J Rees, Zane B Andrews, Jeffrey S Davies
Parkinson's disease is a common age-related neurodegenerative disorder affecting 10 million people worldwide, but the mechanisms underlying its pathogenesis are still unclear. The disease is characterised by dopamine nerve cell loss in the mid-brain and intra-cellular accumulation of α-synuclein that results in motor and non-motor dysfunction. In this review, we discuss the neuroprotective effects of the stomach hormone, ghrelin, in models of Parkinson's disease. Recent findings suggest that it may modulate mitochondrial function and autophagic clearance of impaired organelle in response to changes in cellular energy balance...
December 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29276054/drd3-signaling-in-the-lateral-septum-mediates-early-life-stress-induced-social-dysfunction
#12
Sora Shin, Horia Pribiag, Varoth Lilascharoen, Daniel Knowland, Xiao-Yun Wang, Byung Kook Lim
Early life stress (ELS) in the form of child abuse/neglect is associated with an increased risk of developing social dysfunction in adulthood. Little is known, however, about the neural substrates or the neuromodulatory signaling that govern ELS-induced social dysfunction. Here, we show that ELS-induced downregulation of dopamine receptor 3 (Drd3) signaling and its corresponding effects on neural activity in the lateral septum (LS) are both necessary and sufficient to cause social abnormalities in adulthood...
December 14, 2017: Neuron
https://www.readbyqxmd.com/read/29250896/changes-in-neuronal-activity-of-cortico-basal-ganglia-thalamic-networks-induced-by-acute-dopaminergic-manipulations-in-rats
#13
Nedjeljka Ivica, Ulrike Richter, Joel Sjöbom, Ivani Brys, Martin Tamtè, Per Petersson
The basal ganglia are thought to be particularly sensitive to changes in dopaminergic tone, and the realization that reduced dopaminergic signaling causes pronounced motor dysfunction is the rationale behind dopamine replacement therapy in Parkinson's disease. It has however proven difficult to identify which neurophysiological changes that ultimately lead to motor dysfunctions. To clarify this, we have here recorded neuronal activity throughout the cortico-basal ganglia-thalamic circuits in freely behaving rats during periods of immobility following acute dopaminergic manipulations, involving both vesicular depletion and antagonism of D1 and D2 type dopamine receptors...
December 18, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29249680/dopaminergic-polymorphisms-associated-with-medication-responsiveness-of-gait-in-parkinson-s-disease
#14
Nathaniel S Miller, Kelvin L Chou, Nicolaas I Bohnen, Martijn L T M Müller, Rachael D Seidler
BACKGROUND: Gait dysfunction is a common symptom of Parkinson's disease that can cause significant disability and put patients at risk for falls. These symptoms show variable responsiveness to dopaminergic therapy. OBJECTIVE: To determine whether dopaminergic (rs1076560 DRD2 G > T and rs4680 catechole-o-methyltranspherase (COMT) Val158Met) or brain derived neurotrophic factor (rs6265 BDNF Val66Met) genetic polymorphisms are associated with gait function and medication responsiveness in Parkinson's disease...
December 12, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29248177/a-peek-into-parkinson-s-disease-progression-through-human-dopamine-neurons-in-a-dish
#15
Nan Yang, Zhenyu Yue
Using induced human dopamine (DA) neurons, a study by Burbulla and colleagues demonstrated a toxic cascade of cellular dysfunctions which may underlie Parkinson's disease (PD) progression. Their findings reveal what could be the causal relationship between multiple pathogenic pathways in human neurons obtained from idiopathic and familial cases, and suggest novel targets for therapeutic intervention.
December 13, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/29246613/clinical-management-of-tardive-dyskinesia-five-steps-to-success
#16
REVIEW
Leslie Citrome
Tardive dyskinesia (TD) has long been thought to be a generally irreversible consequence of the use of dopamine receptor blocking agents. There is now an opportunity to successfully manage this condition with agents approved by the US Food and Drug Administration. This is important because TD has not been eliminated with the use of second-generation antipsychotics, and the expansion of antipsychotics to treat conditions other than schizophrenia has resulted in millions of additional individuals at risk for developing TD...
December 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29245933/mir-193-targets-aldh2-and-contributes-to-toxic-aldehyde-accumulation-and-tyrosine-hydroxylase-dysfunction-in-cerebral-ischemia-reperfusion-injury
#17
Li Mao, Mei-Ling Zuo, Guo-Huang Hu, Xiao-Ming Duan, Zhong-Bao Yang
MicroRNAs (miRNAs, miR) play a fundamental role in cerebral ischemia/reperfusion (I/R) injury. However, the role of miRNAs in toxic aldehyde and tyrosine accumulation is not fully elucidated. We constructed a cerebral I/R rat model and found that overexpression of miR-193 was associated with the accumulation of 4-Hydroxynonenal (4-HNE), Malondialdehyde (MDA), and tyrosine, and with the decrease of aldehyde dehydrogenase (ALDH2), tyrosine hydroxylase (TH), and dopamine. To unveil the molecular mechanism of the miR-193-mediated phenotype in I/R injury as described above, we performed bioinformatic analysis and found that ALDH2 was a potential target of miR-193...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29234453/an-association-study-of-taq1a-ankk1-and-c957t-and-%C3%A2-141c-drd2-polymorphisms-in-adults-with-internet-gaming-disorder-a-pilot-study
#18
Soo-Hyun Paik, Mi Ran Choi, Su Min Kwak, Sol Hee Bang, Ji-Won Chun, Jin-Young Kim, Jihye Choi, Hyun Cho, Jo-Eun Jeong, Dai-Jin Kim
Background: Though Internet gaming disorder (IGD) is considered to share similar genetic vulnerability with substance addictions, little has been explored about the role of the genetic variants on IGD. This pilot study was designed to investigate the association of the Taq1A polymorphism of the ankyrin repeat and kinase domain containing 1 (ANKK1) gene and C957T and - 141C of the dopamine D2 receptor (DRD2) with IGD and their role on the personality and temperament traits in IGD among adult population...
2017: Annals of General Psychiatry
https://www.readbyqxmd.com/read/29233065/understanding-the-role-of-glycogen-synthase-kinase-3-in-l-dopa-induced-dyskinesia-in-parkinson-s-disease
#19
Hojin Choi, Seong-Ho Koh
Levodopa (L-DOPA) is the most commonly used drug for Parkinson's disease (PD), but its long-term use is associated with various complications, including L-DOPA-induced dyskinesia (LID). Many studies have suggested that L-DOPA neurotoxicity and LID are associated with glycogen synthase kinase-3 (GSK-3) activation. Areas covered: LID is caused by striatal dopamine (DA) denervation in PD and pulsatile L-DOPA treatment. These factors lead to dysregulated DA transmission, abnormal intracellular signaling and transcription factors in striatal neurons, and altered gene expression and plasticity at corticostriatal synapses...
December 15, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29231773/molecular-imaging-of-autism-spectrum-disorder
#20
Brian Jaeho Hwang, Mona Adel Mohamed, James Robert Brašić
Autism spectrum disorder (ASD) is a condition with onset in early childhood characterized by marked deficits in interpersonal interactions and communication and by a restricted and repetitive range of interests and activities. This review points out key recent findings utilizing molecular imaging including magnetic resonance spectroscopy (MRS) and nuclear neuroimaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). MRS indicates an excitatory/inhibitory imbalance in high-functioning autism...
December 12, 2017: International Review of Psychiatry
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