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https://www.readbyqxmd.com/read/27915183/search-for-new-potential-anticonvulsants-with-anxiolytic-and-antidepressant-properties-among-derivatives-of-4-4-diphenylpyrrolidin-2-one
#1
Katarzyna Malawska, Aleksandra Rak, Beata Gryzło, Kinga Sałat, Małgorzata Michałowska, Elżbieta Żmudzka, Krzysztof Lodarski, Barbara Malawska, Katarzyna Kulig
BACKGROUND: The aim of this study was to synthesize a series of new N-Mannich bases derived from 4,4-diphenylpyrrolidin-2-one having differently substituted 4-phenylpiperazines as potential anticonvulsant agents with additional (beneficial) pharmacological properties. METHODS: The target compounds 8-12 were prepared in one step from the 4-substituted phenylpiperazines, paraformaldehyde, and synthesized 4,4-diphenylpyrrolodin-2-one (7) by a Mannich-type reaction...
September 22, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27915043/involvement-of-bdnf-trkb-signaling-in-the-effect-of-diphenyl-diselenide-on-motor-function-in-a-parkinson-s-disease-rat-model
#2
Tuane Bazanella Sampaio, Simone Pinton, Juliana Trevisan da Rocha, Bibiana Mozzaquatro Gai, Cristina Wayne Nogueira
Parkinson's disease is a progressive neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons. Diphenyl diselenide [(PhSe)2] is a compound with pharmacological proprieties, such as antidepressant and neuroprotective. Therefore, this study investigated whether (PhSe)2 reverses motor impairment and neurochemical alterations in a model of Parkinson's disease induced by 6-hydroxydopamine (6-OHDA) in rats. For this, male Wistar rats received 20μg/3μl of 6-OHDA or vehicle into the right striatum...
November 30, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27911409/measuring-progressive-neurological-disability-in-a-mouse-model-of-multiple-sclerosis
#3
Francesca Gilli, Darlene B Royce, Andrew R Pachner
After intracerebral infection with the Theiler's Murine Encephalomyelitis Virus (TMEV), susceptible SJL mice develop a chronic-progressive demyelinating disease, with clinical features similar to the progressive forms of multiple sclerosis (MS). The mice show progressive disability with loss of motor and sensory functions, which can be assessed with multiple apparatuses and protocols. Among them, the Rotarod performance test is a very common behavioral test, its advantage being that it provides objective measurements, but it is often used assuming that it is straightforward and simple...
November 14, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#4
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905041/new-xymedon-analogues-for-stimulation-of-posttraumatic-regeneration-of-the-spinal-cord-in-rats
#5
T V Povysheva, V E Semenov, I V Galyametdinova, V S Reznik, K S Knni, P E Kolesnikov, Yu A Chelyshev
Effect of systemic administration of synthetic pyrimidine derivatives, xymedon and compounds 29D and 34D, was studied in rats with experimental dosed contusion spinal cord injury. Xymedon promoted recovery of motor function after injury. Compounds 29D and 34D more effectively restored the parameters of open-field and Rotarod tests in comparison with xymedon. Compound 29D more effectively than xymedon maintained the number of Olig2(+) oligodendrocytes in the corticospinal tract and NG2 cells in all investigated areas of the white matter...
December 1, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27895509/effects-of-fentanyl-on-pain-and-motor-behaviors-following-a-collagenase-induced-intracerebral-hemorrhage-in-rats
#6
Laurence Saine, Pierre Hélie, Pascal Vachon
PURPOSE: Intracerebral hemorrhage (IH) and cephalalgia are common consequences of traumatic brain injury. One of the primary obstacles for patient recovery is the paucity of treatments to support an appropriate analgesic protocol. The present study aimed to assess pain and motor behaviors following different doses of fentanyl on a rat model of IH. METHODS: Twenty-one male Sprague Dawley rats underwent a stereotaxic surgery to produce a collagenase-induced IH in the right caudoputamen nucleus...
2016: Journal of Pain Research
https://www.readbyqxmd.com/read/27889925/deletion-of-the-vesicular-acetylcholine-transporter-from-pedunculopontine-laterodorsal-tegmental-neurons-modifies-gait
#7
Helena Janickova, Kaie Rosborough, Mohammed Al-Onaizi, Ornela Kljakic, Monica S Guzman, Robert Gros, Marco A M Prado, Vania F Prado
Postural instability and gait disturbances, common disabilities in the elderly and frequently present in Parkinson's disease (PD), have been suggested to be related to dysfunctional cholinergic signalling in the brainstem. We investigated how long-term loss of cholinergic signalling from mesopontine nuclei influence motor behaviours. We selectively eliminated the vesicular acetylcholine transporter (VAChT) in pedunculopontine and laterodorsal tegmental nuclei cholinergic neurons to generate mice with selective mesopontine cholinergic deficiency (VAChT(E)(n1-Cre-flox/flox) )...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889489/the-drug-candidate-adx71441-is-a-novel-potent-and-selective-positive-allosteric-modulator-of-the-gabab-receptor-with-a-potential-for-treatment-of-anxiety-pain-and-spasticity
#8
Mikhail Kalinichev, Françoise Girard, Hasnaà Haddouk, Mélanie Rouillier, Eric Riguet, Isabelle Royer-Urios, Vincent Mutel, Robert Lütjens, Sonia Poli
Positive allosteric modulation of the GABAB receptor is a promising alternative to direct activation of the receptor as a therapeutic approach for treatment of addiction, chronic pain, anxiety, epilepsy, autism, Fragile X syndrome, and psychosis. Here we describe in vitro and in vivo characterization of a novel, potent and selective GABAB positive allosteric modulator (PAM) N-(5-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)-2-fluorophenyl)acetamide (ADX71441). In vitro, Schild plot and reversibility tests at the target confirmed PAM properties of the compound...
November 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27862616/topical-gabapentin-gel-alleviates-allodynia-and-hyperalgesia-in-the-chronic-sciatic-nerve-constriction-injury-neuropathic-pain-model
#9
M Shahid, F Subhan, N Ahmad, G Ali, S Akbar, K Fawad, R D E Sewell
BACKGROUND: Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. METHODS: Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days...
November 8, 2016: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/27834333/effect-of-lamotrigine-levetiracetam-topiramate-on-neurobehavioural-parameters-oxidative-stress-in-comparison-with-valproate-in-rats
#10
Sudhir Chandra Sarangi, Ashish Kumar Kakkar, Ritesh Kumar, Yogendra Kumar Gupta
BACKGROUND & OBJECTIVES: Though newer antiepileptic drugs are considered safer than conventional antiepileptics, the effects of lamotrigine, levetiracetam and topiramate on neurobehavioural functions are yet to be established. This study evaluated neurobehavioural parameters and oxidative stress markers in brain tissue of rats treated with lamotrigine, levetiracetam and topiramate compared to sodium valproate . METHODS: Five groups of male Wistar rats were treated respectively with normal saline (control), sodium valproate (370 mg/kg), lamotrigine (50 mg/kg), levetiracetam (310 mg/kg) and topiramate (100 mg/kg) for 45 days...
July 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/27829998/the-effects-and-mechanism-of-estrogen-on-rats-with-parkinson-s-disease-in-different-age-groups
#11
Xue-Zhong Li, Chen-Yan Sui, Qiang Chen, Yuan-Su Zhuang, Hong Zhang, Xiao-Ping Zhou
OBJECTIVE: In order to investigate the effect and mechanism of estrogen in rotenone-induced Parkinson's disease (PD) rats in different age groups. METHODS: we established rat models of PD by rotenone at different interventions. Then, behavioral tests, immunohistochemistry, western blot, high-performance liquid chromatography-electrochemical detector (HPLC-ECD) and electron microscopy were performed. RESULTS: Results revealed the following: (1) Rotenone significantly reduced rotarod latencies in senile rats, prolonged their climbing pole time, and decreased TH positive cells, DA and its metabolite, DOPAC...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27815397/new-strategy-that-delays-progression-of-amyotrophic-lateral-sclerosis-in-g1h-g93a-transgenic-mice-oral-administration-of-xanthine-oxidoreductase-inhibitors-that-are-not-substrates-for-the-purine-salvage-pathway
#12
Shinsuke Kato, Masako Kato, Teruo Kusano, Takeshi Nishino
Amyotrophic lateral sclerosis (ALS), Lou Gehrig's disease, is a progressive fatal neurodegenerative disease that involves both upper and lower motor neurons. We orally administered 4 xanthine oxidoreductase (XOR) inhibitors to G1H-G93A mice carrying 25 transgene copy numbers of human mutant G93A superoxide dismutase 1, from 80 days of age. Three nonpurine-analogue inhibitors (TEI-6720: Febuxostat, Y-700 and FYX-051), but not allopurinol with a purine analogue ring (pyrazolo pyrimidine ring), significantly delayed disease onset, prolonged survival and the duration of disease stages, improved clinical signs, and alleviated weight loss...
November 4, 2016: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/27812195/the-cstf2t-polyadenylation-gene-plays-a-sex-specific-role-in-learning-behaviors-in-mice
#13
Jaryse C Harris, Joseph M Martinez, Petar N Grozdanov, Susan E Bergeson, Paula Grammas, Clinton C MacDonald
Polyadenylation is an essential mechanism for the processing of mRNA 3' ends. CstF-64 (the 64,000 Mr subunit of the cleavage stimulation factor; gene symbol Cstf2) is an RNA-binding protein that regulates mRNA polyadenylation site usage. We discovered a paralogous form of CstF-64 called τCstF-64 (Cstf2t). The Cstf2t gene is conserved in all eutherian mammals including mice and humans, but the τCstF-64 protein is expressed only in a subset of mammalian tissues, mostly testis and brain. Male mice that lack Cstf2t (Cstf2t-/- mice) experience disruption of spermatogenesis and are infertile, although female fertility is unaffected...
2016: PloS One
https://www.readbyqxmd.com/read/27809277/the-neuroprotective-properties-of-hericium-erinaceus-in-glutamate-damaged-differentiated-pc12-cells-and-an-alzheimer-s-disease-mouse-model
#14
Junrong Zhang, Shengshu An, Wenji Hu, Meiyu Teng, Xue Wang, Yidi Qu, Yang Liu, Ye Yuan, Di Wang
Hericium erinaceus, an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson's and Alzheimer's disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl₃ combined with d-galactose-induced Alzheimer's disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation...
November 1, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27804148/efficacy-of-phosphodiesterase-4-inhibitors-in-juvenile-batten-disease-cln3
#15
Amy Aldrich, Megan E Bosch, Rachel Fallet, Jessica Odvody, Maria Burkovetskaya, Kakulavarapu V Rama Rao, Jonathan D Cooper, Arlene V Drack, Tammy Kielian
OBJECTIVE: Juvenile neuronal ceroid lipofuscinosis (JNCL), or juvenile Batten disease, is a pediatric lysosomal storage disease caused by autosomal recessive mutations in CLN3, typified by blindness, seizures, progressive cognitive and motor decline, and premature death. Currently, there is no treatment for JNCL that slows disease progression, which highlights the need to explore novel strategies to extend the survival and quality of life of afflicted children. Cyclic adenosine monophosphate (cAMP) is a second messenger with pleiotropic effects, including regulating neuroinflammation and neuronal survival...
November 2, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27796747/neonatal-dexamethasone-treatment-exacerbates-hypoxia-ischemia-induced-white-matter-injury
#16
Chia -Yu Yeh, Che-Ming Yeh, Ting-Hsuan Yu, Kan-Hsun Chang, Chiung-Chun Huang, Kuei-Sen Hsu
Dexamethasone, a synthetic glucocorticoid, has been widely used to prevent or ameliorate morbidity of chronic lung disease in preterm infants with respiratory distress syndrome. Despite its beneficial effect on neonatal lung function, growing concern has arisen about adverse effects of this clinical practice on fetal brain development. We demonstrated previously that neonatal dexamethasone (DEX) treatment may render the newborn brain to be more vulnerable to hypoxia/ischemia (HI)-induced gray matter injury...
October 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27794139/bone-marrow-stromal-cell-therapy-for-ischemic-stroke-a-meta-analysis-of-randomized-control-animal-trials
#17
Qing Wu, Yuexiang Wang, Bart M Demaerschalk, Saruna Ghimire, Kay E Wellik, Wenchun Qu
BACKGROUND: Results of animal studies assessing efficacy of bone marrow stromal cell therapy for ischemic stroke remain inconsistent. AIMS: The aims are to assess efficacy of bone marrow stromal cell therapy for ischemic stroke in animal studies. METHODS: Randomized controlled animal trials assessing efficacy of bone marrow stromal cell therapy were eligible. Stroke therapy academic industry round table was used to assess methodologic quality of included studies...
October 28, 2016: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/27789382/effects-of-sesamin-on-motor-and-memory-deficits-in-an-mptp-lesioned-mouse-model-of-parkinson-s-disease-treated-with-l-dopa
#18
T T Zhao, K S Shin, K S Kim, H J Park, H J Kim, K E Lee, M K Lee
The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg)...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27783170/assessment-of-ataxia-phenotype-in-a-new-mouse-model-of-galactose-1-phosphate-uridylyltransferase-galt-deficiency
#19
Wyman Chen, Rose Caston, Bijina Balakrishnan, Anwer Siddiqi, Kamalpreet Parmar, Manshu Tang, Merry Feng, Kent Lai
Despite adequate dietary management, patients with classic galactosemia continue to have increased risks of cognitive deficits, speech dyspraxia, primary ovarian insufficiency, and abnormal motor development. A recent evaluation of a new galactose-1 phosphate uridylyltransferase (GALT)-deficient mouse model revealed reduced fertility and growth restriction. These phenotypes resemble those seen in human patients. In this study, we further assess the fidelity of this new mouse model by examining the animals for the manifestation of a common neurological sequela in human patients: cerebellar ataxia...
October 25, 2016: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/27779080/efficacy-of-ropinirole-loaded-plga-microspheres-for-the-reversion-of-rotenone-induced-parkinsonism
#20
Sofía Negro, Liudmilla Boeva, Karla Slowing, Ana Fernández-Carballido, Luis García-García, Emilia Barcia
A new controlled delivery system is developed for ropinirole (RP) for the treatment of Parkinson´s disease (PD) consisting in PLGA microparticles (MPs) which exhibited in vitro constant release of RP (78.23 µg/day/10 mg MPs) for 19 days. The neuroprotective effects of RP released from MPs are evaluated in SKN-AS cells after exposure to rotenone (20 μM). Cell apoptosis was significantly reduced by RP (100-120 μM). Daily doses of rotenone (2 mg/kg) given i.p. to rats induced neuronal and behavioral changes similar to those of PD...
September 28, 2016: Current Pharmaceutical Design
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