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Synaptive Medical

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https://www.readbyqxmd.com/read/28092666/loss-of-%C3%AE-opioid-receptor-signaling-in-nociceptors-but-not-microglia-abrogates-morphine-tolerance-without-disrupting-analgesia
#1
Gregory Corder, Vivianne L Tawfik, Dong Wang, Elizabeth I Sypek, Sarah A Low, Jasmine R Dickinson, Chaudy Sotoudeh, J David Clark, Ben A Barres, Christopher J Bohlen, Grégory Scherrer
Opioid pain medications have detrimental side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). Tolerance and OIH counteract opioid analgesia and drive dose escalation. The cell types and receptors on which opioids act to initiate these maladaptive processes remain disputed, which has prevented the development of therapies to maximize and sustain opioid analgesic efficacy. We found that μ opioid receptors (MORs) expressed by primary afferent nociceptors initiate tolerance and OIH development...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/27959333/a-single-high-dose-of-dexamethasone-affects-the-phosphorylation-state-of-glutamate-ampa-receptors-in-the-human-limbic-system
#2
M W Lopes, R B Leal, R Guarnieri, M L Schwarzbold, A Hoeller, A P Diaz, G L Boos, K Lin, M N Linhares, J C Nunes, J Quevedo, Z A Bortolotto, H J Markowitsch, S L Lightman, R Walz
Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events...
December 13, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27912162/serotonin-2a-receptor-5-ht2a-gene-promoter-variant-interacts-with-chronic-perceived-stress-to-modulate-resting-parasympathetic-activity-in-humans
#3
Chuan-Chia Chang, Wen-Hui Fang, Hsin-An Chang, Tieh-Ching Chang, Jia-Fwa Shyu, San-Yuan Huang
Decreased resting vagal (parasympathetic) tone is implicated in the development of stress-related disorders, including anxiety and depression. Chronic stress elevates the expression of serotonin 2A receptors (5-HT2A), while activation of 5-HT2A leads to inhibition of parasympathetic synaptic transmission. The T allele of the promoter variant, rs6311 (C>T), of the 5-HT2A gene has been shown to increase the 5-HT2A expression in vitro and to be associated with anxiety and depressive disorders. We thus hypothesized that the 5-HT2A functional polymorphism may influence resting vagal activity among persons with chronically high levels of perceived stress...
February 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27900791/robust-graft-survival-and-normalized-dopaminergic-innervation-do-not-obligate-recovery-in-a-parkinson-disease-patient
#4
Jeffrey H Kordower, Christopher G Goetz, Yaping Chu, Glenda M Halliday, Daniel A Nicholson, Timothy F Musial, David J Marmion, A Jon Stoessl, Vesna Sossi, Thomas B Freeman, C Warren Olanow
OBJECTIVE: The main goal of dopamine cell replacement therapy in Parkinson disease (PD) is to provide clinical benefit mediated by graft survival with nigrostriatal reinnervation. We report a dichotomy between graft structure and clinical function in a patient dying 16 years following fetal nigral grafting. METHODS: A 55-year-old levodopa-responsive woman with PD received bilateral putaminal fetal mesencephalic grafts as part of an NIH-sponsored double-blind sham-controlled trial...
January 2017: Annals of Neurology
https://www.readbyqxmd.com/read/27898323/peripheral-blood-nerve-growth-factor-levels-in-major-psychiatric-disorders
#5
Shuquan Rao, Mónica Martínez-Cengotitabengoa, Yao Yao, Zhiyun Guo, Qi Xu, Suiyan Li, Xianli Zhou, Fuquan Zhang
Nerve growth factor (NGF) plays crucial roles in promoting neural growth and survival, and mediating synaptic and morphological plasticity. Several studies investigated the correlation between peripheral NGF levels and major psychiatric disorders, including schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD); however, the findings were inconsistent. This meta-analysis sought to investigate blood NGF levels in patients with psychiatric disorders compared with healthy subjects and examined potential effects of blood fraction, medication and disease status...
March 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27898073/proteomic-analysis-of-the-postsynaptic-density-implicates-synaptic-function-and-energy-pathways-in-bipolar-disorder
#6
M Föcking, P Dicker, L M Lopez, M Hryniewiecka, K Wynne, J A English, G Cagney, D R Cotter
The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders such as schizophrenia and bipolar disorder. We enriched for this anatomical structure in the anterior cingulate cortex of 16 bipolar disorder samples and 20 controls from the Stanley Medical Research Institute. Unbiased shotgun proteomics incorporating label-free quantitation was used to identify differentially expressed proteins. Quantitative investigation of the PSD identified 2033 proteins, among which 288 were found to be differentially expressed...
November 29, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27886522/increase-in-pas-induced-neuroplasticity-after-a-treatment-course-of-intranasal-ketamine-for-depression-report-of-three-cases-from-a-placebo-controlled-trial
#7
Verònica Gálvez, Stevan Nikolin, Kerrie-Anne Ho, Angelo Alonzo, Andrew A Somogyi, Colleen K Loo
BACKGROUND: Animal studies suggest that neural plasticity may play a role in the antidepressant effects of a single ketamine dose. However, the potential effects of repeated ketamine treatments on human neuroplasticity are unknown. METHODS: This pilot RCT study measured plasticity-induced changes before and after a ketamine course, in three treatment-resistant depressed subjects, who were randomized to receive 8 intranasal treatments of 100mg ketamine or 4.5mg midazolam...
February 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/27866902/the-atypical-antipsychotic-olanzapine-disturbs-depotentiation-by-modulating-machrs-and-impairs-reversal-learning
#8
Woo Seok Song, Jin Hee Cha, Sang Ho Yoon, Young Seon Cho, Kyeong-Yeol Park, Myoung-Hwan Kim
Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27864268/de-novo-gabrg2-mutations-associated-with-epileptic-encephalopathies
#9
Dingding Shen, Ciria C Hernandez, Wangzhen Shen, Ningning Hu, Annapurna Poduri, Beth Shiedley, Alex Rotenberg, Alexandre N Datta, Steffen Leiz, Steffi Patzer, Rainer Boor, Kerri Ramsey, Ethan Goldberg, Ingo Helbig, Xilma R Ortiz-Gonzalez, Johannes R Lemke, Eric D Marsh, Robert L Macdonald
Epileptic encephalopathies are a devastating group of severe childhood onset epilepsies with medication-resistant seizures and poor developmental outcomes. Many epileptic encephalopathies have a genetic aetiology and are often associated with de novo mutations in genes mediating synaptic transmission, including GABAA receptor subunit genes. Recently, we performed next generation sequencing on patients with a spectrum of epileptic encephalopathy phenotypes, and we identified five novel (A106T, I107T, P282S, R323W and F343L) and one known (R323Q) de novo GABRG2 pathogenic variants (mutations) in eight patients...
January 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27863874/successful-autologous-haematopoietic-stem-cell-transplantation-for-refractory-myasthenia-gravis-a-case-report
#10
Irene Håkansson, Anna Sandstedt, Fredrik Lundin, Håkan Askmark, Ritva Pirskanen, Kristina Carlson, Fredrik Piehl, Hans Hägglund
Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation...
September 28, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/27852961/effect-of-antipsychotic-pharmacotherapy-on-clinical-outcomes-of-intermittent-theta-burst-stimulation-for-refractory-depression
#11
Laura Schulze, Gary Remington, Peter Giacobbe, Sidney H Kennedy, Daniel M Blumberger, Zafiris J Daskalakis, Jonathan Downar
Theta-burst stimulation is an emerging protocol for repetitive transcranial magnetic stimulation that takes 1-3 min to administer, yet offers equal/superior potency to conventional protocols lasting 30-60 min. However, preclinical evidence suggests that D2 receptor blockade may abolish the acute effects of theta-burst stimulation on synaptic facilitation or inhibition. As many patients presenting for repetitive transcranial magnetic stimulation are taking antipsychotic medications as augmentation for treatment-resistant depression, this finding is potentially concerning for the implementation of theta-burst stimulation in clinical settings...
November 9, 2016: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/27822050/autoimmune-encephalitis-in-psychiatric-institutions-current-perspectives
#12
REVIEW
Chloe Bost, Olivier Pascual, Jérôme Honnorat
Autoimmune encephalitis is a rare and newly described group of diseases involving autoantibodies directed against synaptic and neuronal cell surface antigens. It comprises a wide range of neuropsychiatric symptoms. Sensitive and specific diagnostic tests such as cell-based assay are primordial for the detection of neuronal cell surface antibodies in patients' cerebrospinal fluid or serum and determine the treatment and follow-up of the patients. As neurological symptoms are fairly well described in the literature, this review focuses on the nature of psychiatric symptoms occurring at the onset or during the course of the diseases...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27799918/magnetoencephalography-for-the-detection-of-intervention-effects-of-a-specific-nutrient-combination-in-patients-with-mild-alzheimer-s-disease-results-from-an-exploratory-double-blind-randomized-controlled-study
#13
Elisabeth C W van Straaten, Hanneke de Waal, Marieke M Lansbergen, Philip Scheltens, Fernando Maestu, Rafal Nowak, Arjan Hillebrand, Cornelis J Stam
Synaptic loss is an early pathological finding in Alzheimer's disease (AD) and correlates with memory impairment. Changes in macroscopic brain activity measured with electro- and magnetoencephalography (EEG and MEG) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials. EEG peak frequency and functional networks have shown, in addition to improved memory performance, to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn(®) Connect, which is designed to enhance synapse formation and function...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27786169/therapeutic-potential-of-transcranial-focused-ultrasound-for-rett-syndrome
#14
Shih-Jen Tsai
Rett syndrome (RTT) is a severe neurodevelopmental disorder occurring almost exclusively in females and is caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2) in the majority of cases. MeCP2 is essential for the normal function of nerve cells, including neuronal development, maturation, and synaptic activity. RTT is characterized by normal early development followed by autistic-like features, slowed brain and head growth, gait abnormalities, seizures, breathing irregularities, and cognitive disabilities...
October 27, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27784811/rapid-and-lasting-enhancement-of-dopaminergic-modulation-at-the-hippocampal-mossy-fiber-synapse-by-electroconvulsive-treatment
#15
Katsunori Kobayashi, Yuki Imoto, Fumi Yamamoto, Mayu Kawasaki, Miyuki Ueno, Eri Segi-Nishida, Hidenori Suzuki
: Electroconvulsive therapy (ECT) is an established effective treatment for medication-resistant depression with the rapid onset of action. However, its cellular mechanism of action has not been revealed. We have previously shown that chronic antidepressant drug treatments enhance dopamine D1-like receptor-dependent synaptic potentiation at the hippocampal mossy fiber (MF)-CA3 excitatory synapse. In this study we show that ECT-like treatments in mice also have marked effects on the dopaminergic synaptic modulation...
January 1, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27784625/nicotine-induced-neuroplasticity-counteracts-the-effect-of-schizophrenia-linked-neuregulin-1-signaling-on-nmdar-function-in-the-rat-hippocampus
#16
Yoshihiko Yamazaki, Katumi Sumikawa
A high rate of heavy tobacco smoking among people with schizophrenia has been suggested to reflect self-medication and amelioration of cognitive dysfunction, a core feature of schizophrenia. NMDAR hypofunction is hypothesized to be a mechanism of cognitive dysfunction, and excessive schizophrenia-linked neuregulin 1 (NRG1) signaling through its receptor ErbB4 can suppress NMDAR function by preventing Src-mediated enhancement of NMDAR responses. Here we investigated whether chronic nicotine exposure in rats by subcutaneous injection of nicotine (0...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27753696/antiepileptic-drugs-under-investigation-for-treatment-of-focal-epilepsy
#17
REVIEW
Pasquale Striano, Vincenzo Belcastro, Antonietta Coppola, Carlo Minetti, Salvatore Striano
INTRODUCTION: Despite optimal medical treatment, up to 30% of patients with epilepsy continue to experience recurrent seizures, and the challenge for new more efficacious and better-tolerated drugs is continuing. New antiepileptic drugs include the evolution of preexisting drugs and new compounds identified through the investigation of additional molecular targets, such as SV2A synaptic vesicle protein, voltage-gated potassium channels, ionotropic and metabotropic glutamate receptors, and gap junctions...
November 2016: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/27750209/an-antioxidant-specifically-targeting-mitochondria-delays-progression-of-alzheimer-s-disease-like-pathology
#18
Natalia A Stefanova, Natalia A Muraleva, Kseniya Yi Maksimova, Ekaterina A Rudnitskaya, Elena Kiseleva, Darya V Telegina, Nataliya G Kolosova
Mitochondrial aberrations are observed in human Alzheimer's disease (AD) and in medical conditions that increase the risk of this disorder, suggesting that mitochondrial dysfunction may contribute to pathophysiology of AD. Here, using OXYS rats that simulate key characteristics of sporadic AD, we set out to determine the role of mitochondria in the pathophysiology of this disorder. OXYS rats were treated with a mitochondria-targeted antioxidant SkQ1 from age 12 to 18 months, that is, during active progression of AD-like pathology in these animals...
October 6, 2016: Aging
https://www.readbyqxmd.com/read/27730463/the-role-of-the-vagal-nucleus-tractus-solitarius-in-the-therapeutic-effects-of-obesity-surgery-and-other-interventional-therapies-on-type-2-diabetes
#19
Claudio Blasi
The current treatment for obesity-related type 2 diabetes is not able to achieve sufficient metabolic control. New remission prospects have been offered through bariatric surgery and other interventional therapies. The aim of the study is to illustrate the mechanism by which such therapies affect the autonomic system, in particular the afferent vagal activity. The first and most important terminal of this activity is the brainstem vagal nucleus tractus solitarius. Its function, on which the vagal efferent inputs that control the splanchnic organs depend, is conditioned by the level of synaptic transmission within it...
October 11, 2016: Obesity Surgery
https://www.readbyqxmd.com/read/27702909/transcriptome-analysis-of-trigeminal-ganglia-following-masseter-muscle-inflammation-in-rats
#20
Man-Kyo Chung, Jennifer Park, Jamila Asgar, Jin Y Ro
BACKGROUND: Chronic pain in masticatory muscles is a major medical problem. Although mechanisms underlying persistent pain in masticatory muscles are not fully understood, sensitization of nociceptive primary afferents following muscle inflammation or injury contributes to muscle hyperalgesia. It is well known that craniofacial muscle injury or inflammation induces regulation of multiple genes in trigeminal ganglia, which is associated with muscle hyperalgesia. However, overall transcriptional profiles within trigeminal ganglia following masseter inflammation have not yet been determined...
2016: Molecular Pain
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