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Drug induced neurological disorders

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https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#1
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28209738/optogenetic-low-frequency-stimulation-of-specific-neuronal-populations-abates-ictogenesis
#2
Zahra Shiri, Maxime Lévesque, Guillaume Etter, Frédéric Manseau, Sylvain Williams, Massimo Avoli
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one third of mesial temporal lobe epilepsy patients. Here, we established the efficacy of cell type-specific low-frequency stimulation (LFS) in controlling ictogenesis in the mouse entorhinal cortex (EC) in an in vitro brain slice preparation. Specifically, we used 1 Hz optogenetic stimulation of Ca(2+)/calmodulin-dependent protein kinase II-positive principal cells as well as of parvalbumin- or somatostatin-positive interneurons to study the effects of such repetitive activation on epileptiform discharges induced by 4-aminopyridine...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28208696/valproate-attenuates-endoplasmic-reticulum-stress-induced-apoptosis-in-sh-sy5y-cells-via-the-akt-gsk3%C3%AE-signaling-pathway
#3
Zhengmao Li, Fenzan Wu, Xie Zhang, Yi Chai, Daqing Chen, Yuetao Yang, Kebin Xu, Jiayu Yin, Rui Li, Hongxue Shi, Zhouguang Wang, Xiaokun Li, Jian Xiao, Hongyu Zhang
Endoplasmic reticulum (ER) stress-induced apoptosis plays an important role in a range of neurological disorders, such as neurodegenerative diseases, spinal cord injury, and diabetic neuropathy. Valproate (VPA), a typical antiepileptic drug, is commonly used in the treatment of bipolar disorder and epilepsy. Recently, VPA has been reported to exert neurotrophic effects and promote neurite outgrowth, but its molecular mechanism is still unclear. In the present study, we investigated whether VPA inhibited ER stress and promoted neuroprotection and neuronal restoration in SH-SY5Y cells and in primary rat cortical neurons, respectively, upon exposure to thapsigargin (TG)...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28194443/sustained-inflammation-after-pericyte-depletion-induces-irreversible-blood-retina-barrier-breakdown
#4
Shuntaro Ogura, Kaori Kurata, Yuki Hattori, Hiroshi Takase, Toshina Ishiguro-Oonuma, Yoonha Hwang, Soyeon Ahn, Inwon Park, Wataru Ikeda, Sentaro Kusuhara, Yoko Fukushima, Hiromi Nara, Hideto Sakai, Takashi Fujiwara, Jun Matsushita, Masatsugu Ema, Masanori Hirashima, Takashi Minami, Masabumi Shibuya, Nobuyuki Takakura, Pilhan Kim, Takaki Miyata, Yuichiro Ogura, Akiyoshi Uemura
In the central nervous system, endothelial cells (ECs) and pericytes (PCs) of blood vessel walls cooperatively form a physical and chemical barrier to maintain neural homeostasis. However, in diabetic retinopathy (DR), the loss of PCs from vessel walls is assumed to cause breakdown of the blood-retina barrier (BRB) and subsequent vision-threatening vascular dysfunctions. Nonetheless, the lack of adequate DR animal models has precluded disease understanding and drug discovery. Here, by using an anti-PDGFRβ antibody, we show that transient inhibition of the PC recruitment to developing retinal vessels sustained EC-PC dissociations and BRB breakdown in adult mouse retinas, reproducing characteristic features of DR such as hyperpermeability, hypoperfusion, and neoangiogenesis...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28182332/challenging-the-great-vascular-wall-can-we-envision-a-simple-yet-comprehensive-therapy-for-stroke
#5
Marta Machado-Pereira, Tiago Santos, Lino Ferreira, Liliana Bernardino, Raquel Ferreira
Stroke is a leading cause of death in adult life, closely behind ischemic heart disease, and causes a significant and abiding socioeconomic burden. However, current therapies are not able to ensure full neurologic and/or sequelae-free recovery to all stroke survivors. We believe treatment efficacy and patient rehabilitation could be enhanced significantly by targeting blood-brain barrier (BBB) deregulation and inflammation-induced barrier loss occurring after stroke. In this pathological context, bone marrow-derived endothelial progenitor cells (EPC) enter the bloodstream towards the lesion site but their insufficient numbers and impaired angiogenic ability compromise neurovascular regeneration...
February 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28137434/copper-mediated-dna-damage-by-the-neurotransmitter-dopamine-and-l-dopa-a-pro-oxidant-mechanism
#6
Nida Rehmani, Atif Zafar, Hussain Arif, Sheikh Mumtaz Hadi, Altaf A Wani
Oxidative DNA damage has been implicated in the pathogenesis of neurological disorders, cancer and ageing. Owing to the established link between labile copper concentrations and neurological diseases, it is critical to explore the interactions of neurotransmitters and drug supplements with copper. Herein, we investigate the pro-oxidant DNA damage induced by the interaction of L-DOPA and dopamine (DA) with copper. The DNA binding affinity order of the compounds has been determined by in silico molecular docking...
January 28, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28132834/human-ipsc-derived-neural-progenitors-are-an-effective-drug-discovery-model-for-neurological-mtdna-disorders
#7
Carmen Lorenz, Pierre Lesimple, Raul Bukowiecki, Annika Zink, Gizem Inak, Barbara Mlody, Manvendra Singh, Marcus Semtner, Nancy Mah, Karine Auré, Megan Leong, Oleksandr Zabiegalov, Ekaterini-Maria Lyras, Vanessa Pfiffer, Beatrix Fauler, Jenny Eichhorst, Burkhard Wiesner, Norbert Huebner, Josef Priller, Thorsten Mielke, David Meierhofer, Zsuzsanna Izsvák, Jochen C Meier, Frédéric Bouillaud, James Adjaye, Markus Schuelke, Erich E Wanker, Anne Lombès, Alessandro Prigione
Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation. NPCs derived in this way from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C) showed defective ATP production and abnormally high mitochondrial membrane potential (MMP), plus altered calcium homeostasis, which represents a potential cause of neural impairment...
January 25, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28130052/pharmacological-activation-of-the-neurotensin-receptor-1-abrogates-the-methamphetamine-induced-striatal-apoptosis-in-the-mouse-brain
#8
Qingkun Liu, Ariela Hazan, Eddie Grinman, Jesus A Angulo
Methamphetamine (METH) is a widely abused psychostimulant displaying potent addictive and neurotoxic properties. METH induces neurotoxicity of dopaminergic terminals and striatal neurons in the striatum. Despite much information on neurotransmitters, the role of neuropeptides is poorly understood. In this study, we investigated the role of the neuropeptide neurotensin on the METH-induced apoptosis of some striatal neurons in mice. We observed that a single injection of METH (30 mg/kg, ip) induced the loss of approximately 15% of striatal neurons...
January 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28128334/protein-kinase-c-%C3%AE-a-new-target-therapy-to-prevent-the-long-term-atypical-antipsychotics-induced-weight-gain
#9
Alessandro Rimessi, Chiara Pavan, Elli Ioannidi, Federica Nigro, Claudia Morganti, Alberto Brugnoli, Francesco Longo, Chiara Gardin, Letizia Ferroni, Michele Morari, Vincenzo Vindigni, Barbara Zavan, Paolo Pinton
Antipsychotic drugs are currently used in clinical practice for a variety of mental disorders. Among them, clozapine is the most effective medication for treatment-resistant schizophrenia and is most helpful in controlling aggression and the suicidal behavior in schizophrenia and schizoaffective disorder. Although clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side effects, it is well-known for the weight gain and metabolic side effects, which expose the patient to a greater risk of cardiovascular disorders, premature death, as well as psychosocial issues leading to non-adherence to therapy...
January 27, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28126506/-other-causes-of-parkinsonism
#10
Christine Tranchant
Numerous causes may induce parkinsonism, and in case of Parkinsonism, l-dopa resistance, associated neurological signs, early falls, early dysautonomia or early cognitive disorders are the main red flags which should lead to exclude Parkinson's disease. Drug-induced parkinsonism and in young people, Wilson disease, should always be searched. Lower limbs parkinsonism is often due to vascular lesions. Multiple systemic atrophy, supranuclear palsy, Lewy body disease and the rarer corticobasal degeneration, each have specific clinical signs...
January 23, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/28102474/anti-amnestic-effect-of-curcumin-in-combination-with-donepezil-an-anticholinesterase-drug-involvement-of-cholinergic-system
#11
Ayodele Jacob Akinyemi, Ganiyu Oboh, Sunday Idowu Oyeleye, Opeyemi Ogunsuyi
Recently, combination therapy involving cholinesterase (ChE) inhibitor with other neuroprotective agents has shown better desirable effect in the management/prevention of dementia but limited information is available on their effect with dietary polyphenols. Hence, this study sought to assess the combined pretreatment effect of curcumin, the major polyphenolic compound of turmeric (Curcuma longa) rhizomes, with donepezil, a cholinesterase inhibitor, on cognitive function in scopolamine-induced memory impairment in rats...
January 19, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28098253/the-clinically-approved-antiviral-drug-sofosbuvir-inhibits-zika-virus-replication
#12
Carolina Q Sacramento, Gabrielle R de Melo, Caroline S de Freitas, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Miranda, Natalia Fintelman-Rodrigues, Andressa Marttorelli, André C Ferreira, Giselle Barbosa-Lima, Juliana L Abrantes, Yasmine Rangel Vieira, Mônica M Bastos, Eduardo de Mello Volotão, Estevão Portela Nunes, Diogo A Tschoeke, Luciana Leomil, Erick Correia Loiola, Pablo Trindade, Stevens K Rehen, Fernando A Bozza, Patrícia T Bozza, Nubia Boechat, Fabiano L Thompson, Ana M B de Filippis, Karin Brüning, Thiago Moreno L Souza
Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#13
Jaakko J Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina L Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases, including drug addiction and Parkinson's disease. Because of its well established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been studied extensively in various disorders with disturbed dopamine homeostasis. However, the outcomes from preclinical and clinical studies vary, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28066149/neuroprotective-effect-of-lithium-after-pilocarpine-induced-status-epilepticus-in-mice
#14
Namgue Hong, Yun-Sik Choi, Seong Yun Kim, Hee Jung Kim
Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28030918/to-treat-or-not-to-treat-drug-refractory-epilepsy-by-the-ketogenic-diet-that-is-the-question
#15
REVIEW
Marzena Ułamek-Kozioł, Ryszard Pluta, Anna Bogucka-Kocka, Stanisław J Czuczwar
Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory...
23, 2016: Annals of Agricultural and Environmental Medicine: AAEM
https://www.readbyqxmd.com/read/28012058/glutamate-and-brain-glutaminases-in-drug-addiction
#16
Javier Márquez, José A Campos-Sandoval, Ana Peñalver, José M Matés, Juan A Segura, Eduardo Blanco, Francisco J Alonso, Fernando Rodríguez de Fonseca
Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction...
December 23, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27932945/monoaminergic-and-histaminergic-strategies-and-treatments-in-brain-diseases
#17
REVIEW
Giuseppe Di Giovanni, Dubravka Svob Strac, Montse Sole, Mercedes Unzeta, Keith F Tipton, Dorotea Mück-Šeler, Irene Bolea, Laura Della Corte, Matea Nikolac Perkovic, Nela Pivac, Ilse J Smolders, Anna Stasiak, Wieslawa A Fogel, Philippe De Deurwaerdère
The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27931886/neurobiological-after-effects-of-non-invasive-brain-stimulation
#18
REVIEW
G Cirillo, G Di Pino, F Capone, F Ranieri, L Florio, V Todisco, G Tedeschi, K Funke, V Di Lazzaro
BACKGROUND: In recent years, many studies have evaluated the effects of noninvasive brain stimulation (NIBS) techniques for the treatment of several neurological and psychiatric disorders. Positive results led to approval of NIBS for some of these conditions by the Food and Drug Administration in the USA. The therapeutic effects of NIBS have been related to bi-directional changes in cortical excitability with the direction of change depending on the choice of stimulation protocol. Although after-effects are mostly short lived, complex neurobiological mechanisms related to changes in synaptic excitability bear the potential to further induce therapy-relevant lasting changes...
January 2017: Brain Stimulation
https://www.readbyqxmd.com/read/27927955/gpr126-adgrg6-has-schwann-cell-autonomous-and-nonautonomous-functions-in-peripheral-nerve-injury-and-repair
#19
Amit Mogha, Breanne L Harty, Dan Carlin, Jessica Joseph, Nicholas E Sanchez, Ueli Suter, Xianhua Piao, Valeria Cavalli, Kelly R Monk
: Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes are incompletely understood. We previously showed that the adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for SC development and myelination. Interestingly, the expression of Gpr126 is maintained in adult SCs, suggestive of a function in the mature nerve. We therefore investigated the role of Gpr126 in nerve repair by studying an inducible SC-specific Gpr126 knock-out mouse model...
December 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#20
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
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