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https://www.readbyqxmd.com/read/29790360/-current-and-future-pharmacotherapy-of-severe-psychiatric-disorders
#1
Eva Češková
Despite of tremendous development in CNS research, current treatment is suboptimal especially in severe mental disorders. In medicine, there are two main methods of improving the healthcare provided: seeking new treatment procedures and perfecting (optimizing) the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring, but also implementation of general trends into the clinical practice. New pharmacological options include drugs aimed at other than monoaminergic systems and old drugs used before the psychopharmacological era...
2018: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/29789932/the-cognitive-nuances-of-surprising-events-exposure-to-unexpected-stimuli-elicits-firing-variations-in-neurons-of-the-dorsal-ca1-hippocampus
#2
Ornella Valenti, Nace Mikus, Thomas Klausberger
The ability to recognize novel situations is among the most fascinating and vital of the brain functions. A hypothesis posits that encoding of novelty is prompted by failures in expectancy, according to computation matching incoming information with stored events. Thus, unexpected changes in context are detected within the hippocampus and transferred to downstream structures, eliciting the arousal of the dopamine system. Nevertheless, the precise locus of detection is a matter of debate. The dorsal CA1 hippocampus (dCA1) appears as an ideal candidate for operating a mismatch computation and discriminating the occurrence of diverse stimuli within the same environment...
May 22, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29788902/dystonia-deafness-syndrome-caused-by-actb-p-arg183trp-heterozygosity-shows-striatal-dopaminergic-dysfunction-and-response-to-pallidal-stimulation
#3
Inger Marie Skogseid, Oddveig Røsby, Ane Konglund, James P Connelly, Bård Nedregaard, Greg Eigner Jablonski, Nadja Kvernmo, Asbjørg Stray-Pedersen, Joel C Glover
BACKGROUND: Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally...
May 22, 2018: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/29786160/aberrant-learning-in-parkinson-s-disease-a-neurocomputational-study-on-bradykinesia
#4
Mauro Ursino, Chiara Baston
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology...
May 22, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29786072/mptp-driven-nlrp3-inflammasome-activation-in-microglia-plays-a-central-role-in-dopaminergic-neurodegeneration
#5
Eunju Lee, Inhwa Hwang, Sangjun Park, Sujeong Hong, Boreum Hwang, Yoeseph Cho, Junghyun Son, Je-Wook Yu
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the reduction of dopamine levels in the striatum. Although details of the molecular mechanisms underlying dopaminergic neuronal death in PD remain unclear, neuroinflammation is also considered a potent mediator in the pathogenesis and progression of PD. In the present study, we present evidences that microglial NLRP3 inflammasome activation is critical for dopaminergic neuronal loss and the subsequent motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29782864/are-dopamine-receptor-and-transporter-changes-in-rett-syndrome-reflected-in-mecp2-deficient-mice
#6
Dean F Wong, Mary E Blue, James R Brašić, Ayon Nandi, Heather Valentine, Kirstie H Stansfield, Olivier Rousset, Genila Bibat, Mary E Yablonski, Michael V Johnston, Albert Gjedde, SakkuBai Naidu
In the present study we tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D2 receptors (D2 R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1 R and D2 R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D2 R density in the striatum of women with RTT compared to control subjects...
May 18, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29773830/circadian-and-homeostatic-modulation-of-multi-unit-activity-in-midbrain-dopaminergic-structures
#7
Karim Fifel, Johanna H Meijer, Tom Deboer
Although the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical neuronal activity in midbrain ventral-tegmental-area (VTA) and substantia nigra (SN). We found no significant circadian modulation of activity in SN while VTA displayed a low amplitude but significant circadian modulation with increased firing rates during the active phase...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769405/%C3%AE-synuclein-stimulation-of-monoamine-oxidase-b-and-legumain-protease-mediates-the-pathology-of-parkinson-s-disease
#8
Seong Su Kang, Eun Hee Ahn, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Ivette M Sandoval, Susov Dhakal, P Michael Iuvone, Xuebing Cao, Keqiang Ye
Dopaminergic neurodegeneration in Parkinson's disease (PD) is associated with abnormal dopamine metabolism by MAO-B (monoamine oxidase-B) and intracellular α-Synuclein (α-Syn) aggregates, called the Lewy body. However, the molecular relationship between α-Syn and MAO-B remains unclear. Here, we show that α-Syn directly binds to MAO-B and stimulates its enzymatic activity, which triggers AEP (asparagine endopeptidase; legumain) activation and subsequent α-Syn cleavage at N103, leading to dopaminergic neurodegeneration...
May 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29768629/controversial-issues-in-the-management-of-hyperprolactinemia-and-prolactinomas-an-overview-by-the-neuroendocrinology-department-of-the-brazilian-society-of-endocrinology-and-metabolism
#9
Lucio Vilar, Julio Abucham, José Luciano Albuquerque, Luiz Antônio Araujo, Monalisa F Azevedo, Cesar Luiz Boguszewski, Luiz Augusto Casulari, Malebranche B C Cunha Neto, Mauro A Czepielewski, Felipe H G Duarte, Manuel Dos S Faria, Monica R Gadelha, Heraldo M Garmes, Andrea Glezer, Maria Helane Gurgel, Raquel S Jallad, Manoel Martins, Paulo A C Miranda, Renan M Montenegro, Nina R C Musolino, Luciana A Naves, Antônio Ribeiro-Oliveira Júnior, Cíntia M S Silva, Camila Viecceli, Marcello D Bronstein
Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare...
March 2018: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29764970/reinforcement-signaling-of-punishment-versus-relief-in-fruit-flies
#10
Christian König, Afshin Khalili, Mathangi Ganesan, Amrita P Nishu, Alejandra P Garza, Thomas Niewalda, Bertram Gerber, Yoshinori Aso, Ayse Yarali
Painful events establish opponent memories: cues that precede pain are remembered negatively, whereas cues that follow pain, thus coinciding with relief are recalled positively. How do individual reinforcement-signaling neurons contribute to this "timing-dependent valence-reversal?" We addressed this question using an optogenetic approach in the fruit fly. Two types of fly dopaminergic neuron, each comprising just one paired cell, indeed established learned avoidance of odors that preceded their photostimulation during training, and learned approach to odors that followed the photostimulation...
June 2018: Learning & Memory
https://www.readbyqxmd.com/read/29756519/adipose-derived-stem-cells-stimulated-with-n-butylidenephthalide-exhibit-therapeutic-effects-in-a-mouse-model-of-parkinson-s-disease
#11
Kang Chi, Ru-Huei Fu, Yu-Chuen Huang, Shih-Yin Chen, Ching-Ju Hsu, Shinn-Zong Lin, Chi-Tang Tu, Li-Hsun Chang, Ping-An Wu, Shih-Ping Liu
Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29742478/autoimmune-phenotypes-in-schizophrenia-reveal-novel-treatment-targets
#12
REVIEW
Emily G Severance, Faith B Dickerson, Robert H Yolken
Typical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious side effects that impact compliance. Antipsychotic drugs generally target the dopamine pathways with some variation. As research of schizophrenia pathophysiology has shifted away from a strictly dopamine-centric focus, the development of new pharmacotherapies has waned. A field of inquiry with centuries-old roots is gaining traction in psychiatric research circles and may represent a new frontier for drug discovery in schizophrenia...
May 6, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29742425/gat-3-dysfunction-generates-tonic-inhibition-in-external-globus-pallidus-neurons-in-parkinsonian-rodents
#13
Marine Chazalon, Elena Paredes-Rodriguez, Stéphanie Morin, Audrey Martinez, Sofia Cristóvão-Ferreira, Sandra Vaz, Ana Sebastiao, Aude Panatier, Eric Boué-Grabot, Cristina Miguelez, Jérôme Baufreton
The external globus pallidus (GP) is a key GABAergic hub in the basal ganglia (BG) circuitry, a neuronal network involved in motor control. In Parkinson's disease (PD), the rate and pattern of activity of GP neurons are profoundly altered and contribute to the motor symptoms of the disease. In rodent models of PD, the striato-pallidal pathway is hyperactive, and extracellular GABA concentrations are abnormally elevated in the GP, supporting the hypothesis of an alteration of neuronal and/or glial clearance of GABA...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29735704/lrrk2-phosphorylation-of-auxilin-mediates-synaptic-defects-in-dopaminergic-neurons-from-patients-with-parkinson-s-disease
#14
Maria Nguyen, Dimitri Krainc
Recently identified Parkinson's disease (PD) genes involved in synaptic vesicle endocytosis, such as DNAJC6 (auxilin), have further implicated synaptic dysfunction in PD pathogenesis. However, how synaptic dysfunction contributes to the vulnerability of human dopaminergic neurons has not been previously explored. Here, we demonstrate that commonly mutated, PD-linked leucine-rich repeat kinase 2 (LRRK2) mediates the phosphorylation of auxilin in its clathrin-binding domain at Ser627. Kinase activity-dependent LRRK2 phosphorylation of auxilin led to differential clathrin binding, resulting in disrupted synaptic vesicle endocytosis and decreased synaptic vesicle density in LRRK2 patient-derived dopaminergic neurons...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29728749/the-role-of-18f-fp-cit-pet-in-differentiation-of-progressive-supranuclear-palsy-and-frontotemporal-dementia-in-the-early-stage
#15
Han Soo Yoo, Seok Jong Chung, Soo-Jong Kim, Jung Su Oh, Jae Seung Kim, Byoung Seok Ye, Young Ho Sohn, Phil Hyu Lee
PURPOSE: The purpose of this study was to evaluate whether the pattern of striatal dopamine transporter (DAT) availability could differentiate between progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD) in the first few years of the disease. METHODS: We enrolled patients who had Parkinsonism and frontal dysfunction and/or language deficit, visited the clinic within 2 years of the onset of symptoms, and had been followed-up for longer than 5 years; thus resulting in 26 patients with PSP and 24 patients with FTD...
May 4, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29727629/losartan-prevents-the-imbalance-between-renal-dopaminergic-and-renin-angiotensin-systems-induced-by-fructose-overload-l-dopa-dopamine-index-as-new-potential-biomarker-of-renal-dysfunction
#16
Natalia Lucía Rukavina Mikusic, Nicolás Martín Kouyoumdzian, Ana Uceda, Julieta Sofía Del Mauro, Marcela Pandolfo, Mariela Mercedes Gironacci, Ana María Puyó, Jorge Eduardo Toblli, Belisario Enrique Fernández, Marcelo Roberto Choi
BACKGROUND: The renin angiotensin system (RAS) and the renal dopaminergic system (RDS) act as autocrine and paracrine systems to regulate renal sodium management and inflammation and their alterations have been associated to hypertension and renal damage. Nearly 30-50% of hypertensive patients have insulin resistance (IR), with a strong correlation between hyperinsulinemia and microalbuminuria. OBJECTIVE: The aim of this study was to demonstrate the existence of an imbalance between RAS and RDS associated to IR, hypertension and kidney damage induced by fructose overload (FO), as well as to establish their prevention, by pharmacological inhibition of RAS with losartan...
May 1, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29726995/the-balance-of-pi3k-and-erk-signaling-is-dysregulated-in-prolactinoma-and-modulated-by-dopamine
#17
Allyson K Roof, Siwanon Jirawatnotai, Tammy Trudeau, Crystal Kuzyk, Margaret E Wierman, Hiroaki Kiyokawa, Arthur Gutierrez-Hartmann
Prolactin-secreting adenomas, or prolactinomas, cause hypogonadism, osteoporosis, and infertility. Although dopamine agonists (DAs) are used clinically to treat prolactinoma, and reduce prolactin secretion via cAMP inhibition, the precise mechanism by which DAs inhibit lactotrope proliferation has not been defined. Here we report the novel finding that PI3K signals through AKT and mTOR to drive proliferation of pituitary somatolactotrope GH4T2 cells. We demonstrate that the DA cabergoline reduces activity of the mTOR effector s6K, and diminishes GH4T2 cell proliferation primarily via activation of the long isoform of the dopamine D2 receptor (D2R)...
May 2, 2018: Endocrinology
https://www.readbyqxmd.com/read/29726015/targeting-the-dopamine-1-receptor-or-its-downstream-signalling-by-inhibiting-phosphodiesterase-1-improves-cognitive-performance
#18
Anton Pekcec, Niklas Schülert, Birgit Stierstorfer, Serena Deiana, Cornelia Dorner-Ciossek, Holger Rosenbrock
BACKGROUND AND PURPOSE: Insufficient prefrontal dopamine 1 (D1) receptor signalling has been linked to cognitive dysfunction in several psychiatric conditions. Because the phosphodiesterase-1 (PDE1) isoform B (PDE1B) is postulated to regulate D1 receptor-dependent signal transduction, this study intended to elucidate the role of PDE1 for cognitive processes reliant on D1 receptor function. EXPERIMENTAL APPROACH: Cognitive performance of the D1 receptor agonist, SKF38393, was studied in the T-maze continuous alternation task and the 5-Choice Serial Reaction Time Task...
May 3, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29719505/cellular-and-molecular-basis-of-neurodegeneration-in-parkinson-disease
#19
REVIEW
Xian-Si Zeng, Wen-Shuo Geng, Jin-Jing Jia, Lei Chen, Peng-Peng Zhang
It has been 200 years since Parkinson disease (PD) was described by Dr. Parkinson in 1817. The disease is the second most common neurodegenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the pathogenesis of PD is still unknown, the research findings from scientists are conducive to understand the pathological mechanisms. It is well accepted that both genetic and environmental factors contribute to the onset of PD. In this review, we summarize the mutations of main seven genes (α-synuclein, LRRK2, PINK1, Parkin, DJ-1, VPS35 and GBA1) linked to PD, discuss the potential mechanisms for the loss of dopaminergic neurons (dopamine metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, impaired autophagy, and deregulation of immunity) in PD, and expect the development direction for treatment of PD...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29713446/evidence-of-oropharyngeal-dysfunction-in-feeding-in-the-rat-rotenone-model-of-parkinson-s-disease
#20
François D H Gould, Andrew Gross, Rebecca Z German, Jason R Richardson
Swallowing disorders in Parkinson's disease are not responsive to dopamine depletion therapy and contribute to morbidity. They are poorly understood owing to a lack of adequate models. We present the first evidence of oropharyngeal changes in a rotenone toxicity model of Parkinson's disease. Rats were recorded while feeding before and after daily rotenone injections at two different doses (2.75 mg/kg and 3 mg/kg). The higher dose had a much more severe parkinsonian phenotype than the low dose. Timing and amplitude of chewing changed, as did the coordination of chewing and swallowing...
2018: Parkinson's Disease
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