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Drug induced neurological disorders

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https://www.readbyqxmd.com/read/28625786/drug-induces-depression-like-phenotypes-and-alters-gene-expression-profiles-in-drosophila
#1
Ming-Di Jiang, Ya Zheng, Jia-Lin Wang, Yu-Feng Wang
BACKGROUND: Major depressive disorder (MDD) is a severe mental illness that affects more than 350 million people worldwide. However, the molecular mechanisms of depression are currently unclear. Studies suggest that Drosophila and humans have similar depression-like symptoms under pressure. In this research, we choose Drosophila melanogaster as the animal model to explore the molecular mechanisms that trigger depression. RESULTS: We found that feeding D. melanogaster with the medium containing Levodopa or Chlorpromazine could induce depression-like phenotypes in both behavioral and biochemical biomarkers, including significantly decreased food intake, mating frequency, serotonin (5-HT) concentration, and increased malondialdehyde (MDA) concentration as well as reduced activity of superoxide dismutase (SOD)...
June 15, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28625586/corticosteroids-in-neurological-disorders-the-dark-side
#2
REVIEW
Dimitrios Parissis, Styliani-Aggeliki Syntila, Panos Ioannidis
Corticosteroids are among the most commonly prescribed drugs by physicians of nearly all medical specialties. Their widespread use in clinical neurology is based either on randomized studies or, most often, on clinical experience and experts' opinion. Besides the well-known adverse effects of corticosteroids, they may also induce or worsen certain neurological disorders. The purpose of this review is to highlight the negative impact of these drugs on these disorders with emphasis on putative pathophysiological mechanisms of this association...
June 15, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28612507/hiv-and-drug-abuse-mediate-astrocyte-senescence-in-a-%C3%AE-catenin-dependent-manner-leading-to-neuronal-toxicity
#3
Chunjiang Yu, Srinivas D Narasipura, Maureen H Richards, Xiu-Ti Hu, Bryan Yamamoto, Lena Al-Harthi
Emerging evidence suggests that cell senescence plays an important role in aging-associated diseases including neurodegenerative diseases. HIV leads to a spectrum of neurologic diseases collectively termed HIV-associated neurocognitive disorders (HAND). Drug abuse, particularly methamphetamine (meth), is a frequently abused psychostimulant among HIV+ individuals and its abuse exacerbates HAND. The mechanism by which HIV and meth lead to brain cell dysregulation is not entirely clear. In this study, we evaluated the impact of HIV and meth on astrocyte senescence using in vitro and several animal models...
June 13, 2017: Aging Cell
https://www.readbyqxmd.com/read/28612111/probable-mechanisms-involved-in-the-antipsychotic-like-activity-of-methyl-jasmonate-in-mice
#4
Olajide S Annafi, Oritoke M Aluko, Anthony T Eduviere, Osarume Omorogbe, Solomon Umukoro
Psychosis is a chronic neuropsychiatric disorder that affects millions of individuals worldwide and impairs the quality of life and productivity of the patients. The clinical efficacy of antipsychotic drugs has been compromised by adverse effects, relapse, and therapeutic failures, thus necessitating search for alternative agents. Methyl jasmonate (MJ) is a bioactive compound reported to have beneficial effects in various neurological disorders. This study was undertaken to investigate the antipsychotic-like effects of MJ in mice...
June 13, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28595536/neuroprotective-effects-of-drug-induced-therapeutic-hypothermia-in-central-nervous-system-diseases
#5
Junwei Ma, Yibin Wang, Zhong Wang, Haiying Li, Zhimin Wang, Gang Chen
Cerebrovascular diseases often cause neurological deficits. Experimental studies have shown that drug-induced hypothermia alleviates brain damage and plays a neuroprotective role, thereby reducing mortality and ameliorating neurological deficits. Therefore, drug-induced hypothermia has an important research value and is further considered in the clinical setting. However, drug-induced hypothermia is also associated with side effects, such as ventricular tachycardia, ventricular fibrillation, suppressed immune function, infection, electrolyte imbalance, glucose metabolism disorders, and skeletal muscle tremor...
June 6, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28593442/remodeling-of-heterochromatin-structure-slows-neuropathological-progression-and-prolongs-survival-in-an-animal-model-of-huntington-s-disease
#6
Junghee Lee, Yu Jin Hwang, Yunha Kim, Min Young Lee, Seung Jae Hyeon, Soojin Lee, Dong Hyun Kim, Sung Jae Jang, Hyoenjoo Im, Sun-Joon Min, Hyunah Choo, Ae Nim Pae, Dong Jin Kim, Kyung Sang Cho, Neil W Kowall, Hoon Ryu
Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. Altered histone modifications and epigenetic mechanisms are closely associated with HD suggesting that transcriptional repression may play a pathogenic role. Epigenetic compounds have significant therapeutic effects in cellular and animal models of HD, but they have not been successful in clinical trials. Herein, we report that dSETDB1/ESET, a histone methyltransferase (HMT), is a mediator of mutant HTT-induced degeneration in a fly HD model...
June 7, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28591739/improvement-of-mitochondrial-function-mediated-the-neuroprotective-effect-of-5-4-hydroxy-3-dimethoxybenzylidene-2-thioxo-4-thiazolidinone-in-rats-with-cerebral-ischemia-reperfusion-injuries
#7
Mingyang Wang, Lu Feng, Ji Zheng, Junya Liu, Shujie Fan, Jun Zhao, Nan Yang, Yanyong Liu, Zhanjun Yang, Caiying Ye, Pingping Zuo
Deficits in mitochondrial function is a critical inducement in the major pathways that drive neuronal cell death in ischemic process particularly. Drugs target to improve the mitochondrial function may be a feasible therapeutic choice in treatment with ischemic diseases. In the present study, we investigated whether 5-(4-hydroxy-3-dimethoxybenzylidene)-2-thioxo-4-thiazolidinone (RD-1), a compound derived from rhodanine, could protect against ischemic neuronal damage via improving mitochondrial function. We tested the neuroprotective effect of RD-1 both in rats modeled by middle cerebral artery occlusion reperfusion in vivo and in primary cortical neurons subjected to hypoxia/reperfusion injury in vitro...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28576415/stem-cell-contributions-to-neurological-disease-modeling-and-personalized-medicine
#8
REVIEW
Nicholas Liang, Cleber A Trujillo, Priscilla D Negraes, Alysson R Muotri, Claudiana Lameu, Henning Ulrich
Human induced pluripotent stem cells (iPSCs) represent a revolutionary tool for disease modeling and drug discovery. The generation of tissue-relevant cell types exhibiting a patient's genetic and molecular background offers the ability to develop individual and effective therapies. In this review, we present some major achievements in the neuroscience field using iPSCs and discuss promising perspectives in personalized medicine. In addition to disease modeling, the understanding of the cellular and molecular basis of neurological disorders is explored, including the discovery of new targets and potential drugs...
May 30, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28559830/choreoathetosis-is-a-possible-adverse-event-of-a-commonly-used-antibiotic
#9
Pornchai Sathirapanya
BACKGROUND: Choreoathetosis (CAS) is attributed to a few neuropsychiatric drugs; however, it is scarcely reported with commonly used antibiotics. AIMS: To present a case of ceftriaxone (CTX)-induced CAS and to perform a literature review. SETTING: A medical teaching hospital. CASE HISTORY: An 83-year-old female with end stage renal disease was prescribed CTX 2 g/day intravenously and doxycycline (DXC) 200 mg/day orally for the treatment of acute community-acquired systemic infection...
January 2017: Case Reports in Neurology
https://www.readbyqxmd.com/read/28553224/docking-studies-and-biological-evaluation-of-a-potential-%C3%AE-secretase-inhibitor-of-3-hydroxyhericenone-f-from-hericium-erinaceus
#10
Chen Diling, Yong Tianqiao, Yang Jian, Zheng Chaoqun, Shuai Ou, Xie Yizhen
Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting approximately more than 5% of the population worldwide over the age 65, annually. The incidence of AD is expected to be higher in the next 10 years. AD patients experience poor prognosis and as a consequence new drugs and therapeutic strategies are required in order to improve the clinical responses and outcomes of AD. The purpose of the present study was to screen a certain number of potential compounds from herbal sources and investigate their corresponding mode of action...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28549128/atad3-gene-cluster-deletions-cause-cerebellar-dysfunction-associated-with-altered-mitochondrial-dna-and-cholesterol-metabolism
#11
Radha Desai, Ann E Frazier, Romina Durigon, Harshil Patel, Aleck W Jones, Ilaria Dalla Rosa, Nicole J Lake, Alison G Compton, Hayley S Mountford, Elena J Tucker, Alice L R Mitchell, Deborah Jackson, Abdul Sesay, Miriam Di Re, Lambert P van den Heuvel, Derek Burke, David Francis, Sebastian Lunke, George McGillivray, Simone Mandelstam, Fanny Mochel, Boris Keren, Claude Jardel, Anne M Turner, P Ian Andrews, Jan Smeitink, Johannes N Spelbrink, Simon J Heales, Masakazu Kohda, Akira Ohtake, Kei Murayama, Yasushi Okazaki, Anne Lombès, Ian J Holt, David R Thorburn, Antonella Spinazzola
Although mitochondrial disorders are clinically heterogeneous, they frequently involve the central nervous system and are among the most common neurogenetic disorders. Identifying the causal genes has benefited enormously from advances in high-throughput sequencing technologies; however, once the defect is known, researchers face the challenge of deciphering the underlying disease mechanism. Here we characterize large biallelic deletions in the region encoding the ATAD3C, ATAD3B and ATAD3A genes. Although high homology complicates genomic analysis of the ATAD3 defects, they can be identified by targeted analysis of standard single nucleotide polymorphism array and whole exome sequencing data...
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28544378/concise-review-induced-pluripotent-stem-cell-based-drug-discovery-for-mitochondrial-disease
#12
REVIEW
Gizem Inak, Carmen Lorenz, Pawel Lisowski, Annika Zink, Barbara Mlody, Alessandro Prigione
High attrition rates and loss of capital plague the drug discovery process. This is particularly evident for mitochondrial disease that typically involves neurological manifestations and is caused by nuclear or mitochondrial DNA defects. This group of heterogeneous disorders is difficult to target because of the variability of the symptoms among individual patients and the lack of viable modeling systems. The use of induced pluripotent stem cells (iPSCs) might significantly improve the search for effective therapies for mitochondrial disease...
May 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28538662/maternal-factors-that-induce-epigenetic-changes-contribute-to-neurological-disorders-in-offspring
#13
REVIEW
Avijit Banik, Deepika Kandilya, Seshadri Ramya, Walter Stünkel, Yap Seng Chong, S Thameem Dheen
It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down's syndrome, Rett syndrome, and later onset of neuropsychological deficits...
May 24, 2017: Genes
https://www.readbyqxmd.com/read/28534925/osmotin-loaded-magnetic-nanoparticles-with-electromagnetic-guidance-for-the-treatment-of-alzheimer-s-disease
#14
Faiz Ul Amin, Ali Kafash Hoshiar, Ton Duc Do, Yeongil Noh, Shahid Ali Shah, Muhammad Sohail Khan, Jungwon Yoon, Myeong Ok Kim
Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain. Here, we describe for the first time the development of a new, pioneering nanotechnology-based drug delivery approach for potential therapies for neurodegenerative diseases, particularly AD. We demonstrated the delivery of fluorescent carboxyl magnetic Nile Red particles (FMNPs) to the brains of normal mice using a functionalized magnetic field (FMF) composed of positive- and negative-pulsed magnetic fields generated by electromagnetic coils...
May 23, 2017: Nanoscale
https://www.readbyqxmd.com/read/28514890/spatial-recognition-test-a-novel-cognition-task-for-assessing-topographical-memory-in-mice
#15
Enes Havolli, Mark Dw Hill, Annie Godley, Pascal Jd Goetghebeur
Dysfunction in topographical memory is a core feature of several neurological disorders. There is a large unmet medical need to address learning and memory deficits as a whole in central nervous system disease. There are considerable efforts to identify pro-cognitive compounds but current methods are either lengthy or labour intensive. Our test used a two chamber apparatus and is based on the preference of rodents to explore novel environments. It was used firstly to assess topographical memory in mice at different retention intervals (RI) and secondly to investigate the effect of three drugs reported to be beneficial for cognitive decline associated with Alzheimer's disease, namely: donepezil, memantine and levetiracetam...
June 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28514657/huntington-s-disease-ipsc-derived-brain-microvascular-endothelial-cells-reveal-wnt-mediated-angiogenic-and-blood-brain-barrier-deficits
#16
Ryan G Lim, Chris Quan, Andrea M Reyes-Ortiz, Sarah E Lutz, Amanda J Kedaigle, Theresa A Gipson, Jie Wu, Gad D Vatine, Jennifer Stocksdale, Malcolm S Casale, Clive N Svendsen, Ernest Fraenkel, David E Housman, Dritan Agalliu, Leslie M Thompson
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28491900/screening-of-conventional-anticonvulsants-in-a-genetic-mouse-model-of-epilepsy
#17
Nicole A Hawkins, Lyndsey L Anderson, Tracy S Gertler, Linda Laux, Alfred L George, Jennifer A Kearney
OBJECTIVE: Epilepsy is a common neurological disorder that affects 1% of the population. Approximately, 30% of individuals with epilepsy are refractory to treatment, highlighting the need for novel therapies. Conventional anticonvulsant screening relies predominantly on induced seizure models. However, these models may not be etiologically relevant for genetic epilepsies. Mutations in SCN1A are a common cause of Dravet Syndrome, a severe epileptic encephalopathy. Dravet syndrome typically begins in infancy with seizures provoked by fever and then progresses to include afebrile pleomorphic seizure types...
May 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28490750/dv21-decreases-excitability-of-cortical-pyramidal-neurons-and-acts-in-epilepsy
#18
Min Xu, Peng Sun, Ying Zhang, Ci-Hang Yang, Xin Wei, Xiao-Xia Ma, Chong-Ren Yang, Kun-Ming Ni, Ying-Jun Zhang, Xiao-Ming Li
Epilepsy is one of the most common neurological disorders and the administration of antiepileptic drugs (AEDs) is the most common treatment. Although there are more than 15 AEDs available, a third of epilepsy patients remain refractory to available drugs, so novel effective drugs are needed. Here, we found that DV21, which is a natural triterpenoid compound extracted from plants of the Asclepiadaceae family, significantly decreased the incidence and stages of seizures in three classical drug-induced acute seizure models in C57BL/6 mice...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28487393/potent-thrombolytic-effect-of-n-acetylcysteine-on-arterial-thrombi
#19
Sara Martinez de Lizarrondo, Clément Gakuba, Bradley A Herbig, Yohann Repessé, Carine Ali, Cécile V Denis, Peter Lenting, Emmanuel Touzé, Scott L Diamond, Denis Vivien, Maxime Gauberti
Background -Platelet crosslinking during arterial thrombosis involves von Willebrand Factor (VWF) multimers. Therefore, proteolysis of VWF appears promising to disaggregate platelet-rich thrombi and restore vessel patency in acute thrombotic disorders such as ischemic stroke, acute coronary syndrome or acute limb ischemia. N-Acetylcysteine (NAC, a clinically approved mucolytic drug) can reduce intrachain disulfide bonds in large polymeric proteins. In the present study, we postulated that NAC might cleave the VWF multimers inside occlusive thrombi, thereby leading to their dissolution and arterial recanalization...
May 9, 2017: Circulation
https://www.readbyqxmd.com/read/28471848/l-borneol-induces-transient-opening-of-the-blood-brain-barrier-and-enhances-the-therapeutic-effect-of-cisplatin
#20
Yi Yin, Liu Cao, Hongfei Ge, Wangsheng Duanmu, Liang Tan, Jichao Yuan, Chen Tunan, Fei Li, Rong Hu, Fabao Gao, Hua Feng
The blood-brain barrier (BBB) protects the central nervous system from external insults by limiting substance diffusion through the endothelial interface. The presence of the BBB makes drug delivery in neurological disorders very challenging. Cisplatin has been shown to be cytotoxic to glioma cells, but substantial limitations exist in its clinical applications due to difficulties in penetration across the BBB. Here, we show that L-borneol, a messenger drug widely used in traditional Chinese medicine, can induce transient disruption of the BBB after 20 min of oral administration...
May 3, 2017: Neuroreport
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