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https://www.readbyqxmd.com/read/28494803/alzheimer-s-disease-dementia-and-stem-cell-therapy
#1
REVIEW
Thomas Duncan, Michael Valenzuela
Alzheimer's disease (AD) represents arguably the most significant social, economic, and medical crisis of our time. Characterized by progressive neurodegenerative pathology, AD is first and foremost a condition of neuronal and synaptic loss. Repopulation and regeneration of depleted neuronal circuitry by exogenous stem cells is therefore a rational therapeutic strategy. This review will focus on recent advances in stem cell therapies utilizing animal models of AD, as well as detailing the human clinical trials of stem cell therapies for AD that are currently undergoing development...
May 12, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28458021/cerebrolysin-alleviates-cognitive-deficits-induced-by-chronic-cerebral-hypoperfusion-by-increasing-the-levels-of-plasticity-related-proteins-and-decreasing-the-levels-of-apoptosis-related-proteins-in-the-rat-hippocampus
#2
Zhijuan Liu, Ming Hu, Peiyuan Lu, Hebo Wang, Qianqian Qi, Jing Xu, Yining Xiao, Mingyue Fan, Yanqiu Jia, Dandan Zhang
The incidence of vascular dementia (VaD) has rapidly increased over the past few decades. Although officially approved medications for VaD remain limited, cerebrolysin (CBL) had preventive and treatment effects on VaD in some clinical trials. However, the underlying mechanisms have not been determined. The aim of this study was to determine whether CBL protects against cognitive deficits in a rat model of VaD induced by chronic cerebral hypoperfusion by increasing the levels of plasticity-related proteins and decreasing the levels of apoptosis-related proteins...
April 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28438600/neurotrophin-receptors-in-the-pathogenesis-diagnosis-and-therapy-of-neurodegenerative-diseases
#3
REVIEW
Jacopo Meldolesi
In the last few years, exciting properties have emerged regarding the activation, signaling, mechanisms of action, and therapeutic targeting of the two types of neurotrophin receptors: the p75(NTR) with its intracellular and extracellular peptides, the Trks, their precursors and their complexes. This review summarizes these new developments, with particular focus on neurodegenerative diseases. Based on the evolving knowledge, innovative concepts have been formulated regarding the pathogenesis of these diseases, especially the Alzheimer's and two other, the Parkinson's and Huntington's diseases...
April 21, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28362388/analyzing-dendritic-morphology-in-columns-and-layers
#4
Chun-Yuan Ting, Philip G McQueen, Nishith Pandya, Evan S McCreedy, Matthew McAuliffe, Chi-Hon Lee
In many regions of the central nervous systems, such as the fly optic lobes and the vertebrate cortex, synaptic circuits are organized in layers and columns to facilitate brain wiring during development and information processing in developed animals. Postsynaptic neurons elaborate dendrites in type-specific patterns in specific layers to synapse with appropriate presynaptic terminals. The fly medulla neuropil is composed of 10 layers and about 750 columns; each column is innervated by dendrites of over 38 types of medulla neurons, which match with the axonal terminals of some 7 types of afferents in a type-specific fashion...
March 23, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28314733/genetics-implicate-common-mechanisms-in-autism-and-schizophrenia-synaptic-activity-and-immunity
#5
REVIEW
Xiaoming Liu, Zhengwei Li, Conghai Fan, Dongli Zhang, Jiao Chen
The diagnosis of debilitating psychiatric disorders like autism spectrum disorder (ASD) and schizophrenia (SCHZ) is on the rise. These are severe conditions that lead to social isolation and require lifelong professional care. Improved diagnosis of ASD and SCHZ provides early access to medication and therapy, but the reality is that the mechanisms and the cellular pathology underlying these conditions are mostly unknown at this time. Although both ASD and SCHZ have strong inherited components, genetic risk seems to be distributed in hundreds of variants, each conferring low risk...
March 17, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28264432/electrophysiological-characterization-of-the-antarease-metalloprotease-from-tityus-serrulatus-venom
#6
Irene Zornetta, Michele Scorzeto, Pablo Victor Mendes Dos Reis, Maria E De Lima, Cesare Montecucco, Aram Megighian, Ornella Rossetto
Scorpions are among the oldest venomous living organisms and the family Buthidae is the largest and most medically relevant one. Scorpion venoms include many toxic peptides, but recently, a metalloprotease from Tityus serrulatus called antarease was reported to be capable of cleaving VAMP2, a protein involved in the neuroparalytic syndromes of tetanus and botulism. We have produced antarease and an inactive metalloprotease mutant in a recombinant form and analyzed their enzymatic activity on recombinant VAMP2 in vitro and on mammalian and insect neuromuscular junction...
February 27, 2017: Toxins
https://www.readbyqxmd.com/read/28258674/ibudilast-a-non%C3%A2-selective-phosphodiesterase-inhibitor-in-brain-disorders
#7
Joanna Schwenkgrub, Małgorzata Zaremba, Dagmara Mirowska-Guzel, Iwona Kurkowska-Jastrzębska
Ibudilast (IBD) is a non‑selective (3, 4, 10, 11) phosphodiesterase (PDE) inhibitor, used mainly as a bronchodilator for the treatment of bronchial asthma. PDE play a central role in cellular function (e.g. differentiation, synaptic plasticity and inflammatory response) by metabolizing cyclic nucleotides. The results from preclinical and clinical studies indicate that IBD has a broader range of action through suppression of pro‑inflammatory cytokines (IL‑6, IL‑1β, TNF‑α), toll‑like receptor 4 blockade (TLR‑4), inhibition of a macrophage migration inhibitory factor (MIF), up‑regulation the anti‑inflammatory cytokine (IL‑10), and promotion of neurotrophic factors (GDNF, NGF, NT‑4)...
March 2, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28251660/neuronal-and-microglial-mechanisms-for-neuropathic-pain-in-the-spinal-dorsal-horn-and-anterior-cingulate-cortex
#8
REVIEW
Makoto Tsuda, Kohei Koga, Tao Chen, Min Zhuo
Neuropathic pain is a debilitating chronic pain condition occurring after damage in the nervous system and is refractory to the currently available treatments. Major challenges include elucidating its mechanisms and developing new medications to treat it. Nerve injury-induced pain hypersensitivity involves aberrant excitability in spinal dorsal horn (SDH) neurons as a consequence of dysfunction of inhibitory interneurons and of hyperactivity of glial cells, especially microglia, the immune cells of the central nervous system...
May 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28241065/repeated-dexamphetamine-treatment-alters-the-dopaminergic-system-and-increases-the-phmri-response-to-methylphenidate
#9
Anouk Schrantee, Jordi L Tremoleda, Marzena Wylezinska-Arridge, Valentine Bouet, Peter Hesseling, Gideon F Meerhoff, Kora M de Bruin, Jan Koeleman, Thomas Freret, Michel Boulouard, Emilie Desfosses, Laurent Galineau, Alessandro Gozzi, François Dauphin, Willy Gsell, Jan Booij, Paul J Lucassen, Liesbeth Reneman
Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function...
2017: PloS One
https://www.readbyqxmd.com/read/28092666/loss-of-%C3%AE-opioid-receptor-signaling-in-nociceptors-but-not-microglia-abrogates-morphine-tolerance-without-disrupting-analgesia
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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