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Article ; Online: Role of 5-HT1A Receptor in Vilazodone-Mediated Suppression of L-DOPA-Induced Dyskinesia and Increased Responsiveness to Cortical Input in Striatal Medium Spiny Neurons in an Animal Model of Parkinson’s Disease

Feras Altwal / Fernando E. Padovan-Neto / Alexandra Ritger / Heinz Steiner / Anthony R. West

Molecules, Vol 26, Iss 5790, p

2021 Volume 5790

Abstract: L-DOPA therapy in Parkinson’s disease (PD) is limited due to emerging L-DOPA-induced dyskinesia ... efficacy of L-DOPA. We investigated vilazodone, a novel multimodal 5-HT agent with SSRI and 5-HTr 1A ... effects of L-DOPA, and underlying mechanisms. We assessed vilazodone effects on L-DOPA-induced dyskinesia ...

Abstract	L-DOPA therapy in Parkinson’s disease (PD) is limited due to emerging L-DOPA-induced dyskinesia. Research has identified abnormal dopamine release from serotonergic (5-HT) terminals contributing to this dyskinesia. Selective serotonin reuptake inhibitors (SSRIs) or 5-HT receptor (5-HTr) agonists can regulate 5-HT activity and attenuate dyskinesia, but they often also produce a loss of the antiparkinsonian efficacy of L-DOPA. We investigated vilazodone, a novel multimodal 5-HT agent with SSRI and 5-HTr 1A partial agonist properties, for its potential to reduce dyskinesia without interfering with the prokinetic effects of L-DOPA, and underlying mechanisms. We assessed vilazodone effects on L-DOPA-induced dyskinesia (abnormal involuntary movements, AIMs) and aberrant responsiveness to corticostriatal drive in striatal medium spiny neurons (MSNs) measured with in vivo single-unit extracellular recordings, in the 6-OHDA rat model of PD. Vilazodone (10 mg/kg) suppressed all subtypes (axial, limb, orolingual) of AIMs induced by L-DOPA (5 mg/kg) and the increase in MSN responsiveness to cortical stimulation (shorter spike onset latency). Both the antidyskinetic effects and reversal in MSN excitability by vilazodone were inhibited by the 5-HTr 1A antagonist WAY-100635, demonstrating a critical role for 5-HTr 1A in these vilazodone actions. Our results indicate that vilazodone may serve as an adjunct therapeutic for reducing dyskinesia in patients with PD.
Keywords	dopamine ; serotonin ; L-DOPA ; striatum ; cortical stimulation ; dyskinesia ; Organic chemistry ; QD241-441
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online ; E-Book: Scientific papers made easy

West, Stuart / Turnbull, L. W.

how to write with clarity and impact in the life sciences

2023

Abstract: This contemporary guide is packed full of expert tips and suggestions which will provide the student reader with the means and motivation to write better scientific papers that are more likely to be read and have impact. ...

Author's details	Stuart West and Lindsay Turnbull
Abstract	This contemporary guide is packed full of expert tips and suggestions which will provide the student reader with the means and motivation to write better scientific papers that are more likely to be read and have impact.
Keywords	Communication in science ; Life sciences/Authorship ; Technical writing
Subject code	808.06657
Language	English
Dates of publication	2023-2023
Size	1 online resource (209 pages)
Publisher	Oxford University Press
Publishing place	Oxford, England
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
ISBN	0-19-195381-4 ; 0-19-267733-0 ; 9780192862785 ; 978-0-19-195381-1 ; 978-0-19-267733-4 ; 0192862782
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: The Multimodal Serotonergic Agent Vilazodone Inhibits L-DOPA-Induced Gene Regulation in Striatal Projection Neurons and Associated Dyskinesia in an Animal Model of Parkinson’s Disease

Feras Altwal / Connor Moon / Anthony R. West / Heinz Steiner

Cells, Vol 9, Iss 2265, p

2020 Volume 2265

Abstract: Levodopa (L-DOPA) treatment in Parkinson’s disease is limited by the emergence of L-DOPA-induced ... agonists could attenuate L-DOPA-induced dyskinesia. We investigated the effects of a novel ... serotonergic agent, vilazodone, which combines SSRI and 5-HT1A partial agonist properties, on L-DOPA-induced behavior ...

Abstract	Levodopa (L-DOPA) treatment in Parkinson’s disease is limited by the emergence of L-DOPA-induced dyskinesia. Such dyskinesia is associated with aberrant gene regulation in neurons of the striatum, which is caused by abnormal dopamine release from serotonin terminals. Previous work showed that modulating the striatal serotonin innervation with selective serotonin reuptake inhibitors (SSRIs) or 5-HT1A receptor agonists could attenuate L-DOPA-induced dyskinesia. We investigated the effects of a novel serotonergic agent, vilazodone, which combines SSRI and 5-HT1A partial agonist properties, on L-DOPA-induced behavior and gene regulation in the striatum in an animal model of Parkinson’s disease. After unilateral dopamine depletion by 6-hydroxydopamine (6-OHDA), rats received repeated L-DOPA treatment (5 mg/kg) alone or in combination with vilazodone (10 mg/kg) for 3 weeks. Gene regulation was then mapped throughout the striatum using in situ hybridization histochemistry. Vilazodone suppressed the development of L-DOPA-induced dyskinesia and turning behavior but did not interfere with the prokinetic effects of L-DOPA (forelimb stepping). L-DOPA treatment drastically increased the expression of dynorphin (direct pathway), 5-HT1B, and zif268 mRNA in the striatum ipsilateral to the lesion. These effects were inhibited by vilazodone. In contrast, vilazodone had no effect on enkephalin expression (indirect pathway) or on gene expression in the intact striatum. Thus, vilazodone inhibited L-DOPA-induced gene regulation selectively in the direct pathway of the dopamine-depleted striatum, molecular changes that are considered critical for L-DOPA-induced dyskinesia. These findings position vilazodone, an approved antidepressant, as a potential adjunct medication for the treatment of L-DOPA-induced motor side effects.
Keywords	dopamine ; serotonin ; gene expression ; L-DOPA ; antidepressant ; striatum ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Saprolegnia diclina IIIA and S. parasitica employ different infection strategies when colonizing eggs of Atlantic salmon, Salmo salar L.

Songe, M M / Willems, A / Wiik-Nielsen, J / Thoen, E / Evensen, Ø / van West, P / Skaar, I

Journal of fish diseases

2015 Volume 39, Issue 3, Page(s) 343–352

Abstract: Here, we address the morphological changes of eyed eggs of Atlantic salmon, Salmo salar L. infected ... scanning electron microscopy. Eggs from six of ten females were infected with S. parasitica, and two females had infections ... with S. diclina clade IIIA; two Saprolegnia isolates remained unidentified. Light microscopy showed S ...

Abstract	Here, we address the morphological changes of eyed eggs of Atlantic salmon, Salmo salar L. infected with Saprolegnia from a commercial hatchery and after experimental infection. Eyed eggs infected with Saprolegnia spp. from 10 Atlantic salmon females were obtained. Egg pathology was investigated by light and scanning electron microscopy. Eggs from six of ten females were infected with S. parasitica, and two females had infections with S. diclina clade IIIA; two Saprolegnia isolates remained unidentified. Light microscopy showed S. diclina infection resulted in the chorion in some areas being completely destroyed, whereas eggs infected with S. parasitica had an apparently intact chorion with hyphae growing within or beneath the chorion. The same contrasting pathology was found in experimentally infected eggs. Scanning electron microscopy revealed that S. parasitica grew on the egg surface and hyphae were found penetrating the chorion of the egg, and re-emerging on the surface away from the infection site. The two Saprolegnia species employ different infection strategies when colonizing salmon eggs. Saprolegnia diclina infection results in chorion destruction, while S. parasitica penetrates intact chorion. We discuss the possibility these infection mechanisms representing a necrotrophic (S. diclina) vs. a facultative biotrophic strategy (S. parasitica).
MeSH term(s)	Animals ; Chorion/pathology ; Chorion/ultrastructure ; Female ; Fish Diseases/parasitology ; Fish Diseases/pathology ; Microscopy, Electron, Scanning ; Ovum/parasitology ; Salmo salar/parasitology ; Saprolegnia/pathogenicity ; Saprolegnia/physiology ; Saprolegnia/ultrastructure ; Species Specificity
Language	English
Publishing date	2015-04-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	432109-1
ISSN	1365-2761 ; 0140-7775
ISSN (online)	1365-2761
ISSN	0140-7775
DOI	10.1111/jfd.12368
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Saprolegnia diclina IIIA and S.Â parasitica employ different infection strategies when colonizing eggs of Atlantic salmon, Salmo salar L

Songe, M M / A Willems / J WiikâNielsen / E Thoen / Ã Evensen / P West / I Skaar

Journal of fish diseases. 2016 Mar., v. 39, no. 3

2016

Abstract: Here, we address the morphological changes of eyed eggs of Atlantic salmon, Salmo salar L. infected ... scanning electron microscopy. Eggs from six of ten females were infected with S.Â parasitica, and two females had infections ... with S.Â diclina clade IIIA; two Saprolegnia isolates remained unidentified. Light microscopy showed S.Â ...

Abstract	Here, we address the morphological changes of eyed eggs of Atlantic salmon, Salmo salar L. infected with Saprolegnia from a commercial hatchery and after experimental infection. Eyed eggs infected with Saprolegnia spp. from 10 Atlantic salmon females were obtained. Egg pathology was investigated by light and scanning electron microscopy. Eggs from six of ten females were infected with S.Â parasitica, and two females had infections with S.Â diclina clade IIIA; two Saprolegnia isolates remained unidentified. Light microscopy showed S.Â diclina infection resulted in the chorion in some areas being completely destroyed, whereas eggs infected with S.Â parasitica had an apparently intact chorion with hyphae growing within or beneath the chorion. The same contrasting pathology was found in experimentally infected eggs. Scanning electron microscopy revealed that S.Â parasitica grew on the egg surface and hyphae were found penetrating the chorion of the egg, and reâemerging on the surface away from the infection site. The two Saprolegnia species employ different infection strategies when colonizing salmon eggs. Saprolegnia diclina infection results in chorion destruction, while S.Â parasitica penetrates intact chorion. We discuss the possibility these infection mechanisms representing a necrotrophic (S.Â diclina) vs. a facultative biotrophic strategy (S.Â parasitica).
Keywords	Salmo salar ; Saprolegnia diclina ; Saprolegnia parasitica ; chorion ; eggs ; females ; hatcheries ; host-parasite relationships ; hyphae ; light microscopy ; parasitism ; salmon ; saprolegniosis ; scanning electron microscopy
Language	English
Dates of publication	2016-03
Size	p. 343-352.
Publishing place	Blackwell Scientific Publications.
Document type	Article
ZDB-ID	432109-1
ISSN	1365-2761 ; 0140-7775
ISSN (online)	1365-2761
ISSN	0140-7775
DOI	10.1111/jfd.12368
Database	NAL-Catalogue (AGRICOLA)

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Conference proceedings ; Online: Saprolegnia diclina IIIA and S. parasitica employ different infection strategies when colonising eggs of Atlantic salmon, Salmo salar L.

Songe, M. / Willems, A. / Wiik-Nielsen, J. / Thoen, E. / Evensen, A. / West, P. van / Skaar, I.

2015

Abstract: ... L. infected with Saprolegnia from a commercial hatchery and after experimental infection. Eyed eggs ... investigated by light and scanning electron microscopy. Eggs from six of ten females were infected with S ... parasitica, and two females had infections with S. diclina clade IIIA; two Saprolegnia isolates remained ...

Abstract	In this study, we addressed the morphological changes of eyed eggs of Atlantic salmon, Salmo salar L. infected with Saprolegnia from a commercial hatchery and after experimental infection. Eyed eggs infected with Saprolegnia spp. from 10 Atlantic salmon females were obtained. Egg pathology was investigated by light and scanning electron microscopy. Eggs from six of ten females were infected with S. parasitica, and two females had infections with S. diclina clade IIIA; two Saprolegnia isolates remained unidentified. Light microscopy showed that S. diclina infection resulted in the chorion in some areas being completely destroyed, whereas eggs infected with S. parasitica had an apparently intact chorion with hyphae growing within or beneath the chorion. The same contrasting pathology was found in experimentally infected eggs. Scanning electron microscopy revealed that S. parasitica grew on the egg surface and hyphae were found penetrating the chorion of the egg, and re-emerging on the surface away from the infection site. The two Saprolegnia species employ different infection strategies when colonizing salmon eggs. Saprolegnia diclina infection results in chorion destruction, while S. parasitica penetrates intact chorion. We discuss the possibility that these infection mechanisms represent a necrotrophic (S. diclina) versus a facultative biotrophic strategy (S. parasitica).
Language	English
Publishing date	2015-10-13T12:22:34Z
Publishing country	fr
Document type	Conference proceedings ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Saprolegnia diclina IIIA and S. parasitica employ different infection strategies when colonizing eggs of Atlantic salmon, Salmo salar L

Songe, M.M. / Willems, A. / Wiik-Nielsen, J. / Thoen, E. / Evensen, A. / West, P. van / Skaar, I.

Journal of Fish Diseases

2015

Abstract	Here, we address the morphological changes of eyed eggs of Atlantic salmon, Salmo salar L. infected with Saprolegnia from a commercial hatchery and after experimental infection. Eyed eggs infected with Saprolegnia spp. from 10 Atlantic salmon females were obtained. Egg pathology was investigated by light and scanning electron microscopy. Eggs from six of ten females were infected with S. parasitica, and two females had infections with S. diclina clade IIIA; two Saprolegnia isolates remained unidentified. Light microscopy showed S. diclina infection resulted in the chorion in some areas being completely destroyed, whereas eggs infected with S. parasitica had an apparently intact chorion with hyphae growing within or beneath the chorion. The same contrasting pathology was found in experimentally infected eggs. Scanning electron microscopy revealed that S. parasitica grew on the egg surface and hyphae were found penetrating the chorion of the egg, and re-emerging on the surface away from the infection site. The two Saprolegnia species employ different infection strategies when colonizing salmon eggs. Saprolegnia diclina infection results in chorion destruction, while S. parasitica penetrates intact chorion. We discuss the possibility these infection mechanisms representing a necrotrophic (S. diclina) vs. a facultative biotrophic strategy (S. parasitica).
Keywords	fish
Language	English
Publishing date	2015-05-29T11:23:38Z
Publisher	Wiley
Publishing country	fr
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Mitochondrial HSP60 (P1 protein) and a HSP70-like protein (mortalin) are major targets for modification during S-(1,1,2,2-tetrafluoroethyl)-L-cysteine-induced nephrotoxicity.

Bruschi, S A / West, K A / Crabb, J W / Gupta, R S / Stevens, J L

The Journal of biological chemistry

1993 Volume 268, Issue 31, Page(s) 23157–23161

Abstract: The potent and site-selective nephrotoxicity of S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC ... in vivo has been associated with difluorothioamidyl-L-lysine formation on critical mitochondrial ... 10 mg/kg, intraperitoneally). Microsequence analysis of the major difluorothioamidyl-L-lysine ...

Abstract	The potent and site-selective nephrotoxicity of S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC) in vivo has been associated with difluorothioamidyl-L-lysine formation on critical mitochondrial target proteins. Dose-response studies in the Fischer 344 rat indicate that five proteins with apparent molecular masses of 99, 84, 66, 52, and 48 kDa are predominantly adducted in vivo after nephrotoxic doses of TFEC (> 10 mg/kg, intraperitoneally). Microsequence analysis of the major difluorothioamidyl-L-lysine proteins indicated that P66 is identical, over 14 NH2-terminal residues, to mitochondrial P1 protein (HSP60, a chaperonin) and that P84 is identical, over 14 residues, to a recently isolated novel member of the HSP70 family known as mortalin. These studies indicate that mitochondrial heat shock proteins are major targets for modification by reactive metabolites of TFEC. The implications of these data in relation to the nephrotoxicity of cysteine conjugates are discussed.
MeSH term(s)	Amino Acid Sequence ; Animals ; Aspartate Aminotransferases/chemistry ; Chaperonins ; Cysteine/analogs & derivatives ; Cysteine/toxicity ; HSP70 Heat-Shock Proteins ; Heat-Shock Proteins/chemistry ; Hydrocarbons, Fluorinated/toxicity ; Kidney/chemistry ; Kidney/drug effects ; Male ; Mitochondria/chemistry ; Mitochondria/drug effects ; Molecular Sequence Data ; Precipitin Tests ; Proteins/chemistry ; Rats ; Rats, Inbred F344
Chemical Substances	HSP70 Heat-Shock Proteins ; Heat-Shock Proteins ; Hydrocarbons, Fluorinated ; Proteins ; mortalin ; S-(1,1,2,2-tetrafluoroethyl)cysteine (94840-66-1) ; Aspartate Aminotransferases (EC 2.6.1.1) ; Chaperonins (EC 3.6.1.-) ; Cysteine (K848JZ4886)
Language	English
Publishing date	1993-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Book ; Online: Ground-based larviciding of s.damnosum s.l breeding sites

World Health Organization / Onchocerciasis Control Programme in West Africa

1991

Abstract: 2 p. ...

Abstract	2 p.
Keywords	Onchocerciasis ; Insecticides ; Simuliidae ; Research Report
Language	English
Publisher	Onchocerciasis Control Programme in West Africa
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Evaluation in a river trial of Carbosulfan 20% ME on S.damnosum s.l. larvae

World Health Organization / Onchocerciasis Control Programme in West Africa

1990

Abstract: 5 p. ...

Abstract	5 p.
Keywords	Carbosulfan ; Onchocerciasis ; Insecticides ; Simuliidae ; Research Report
Language	English
Publisher	Onchocerciasis Control Programme in West Africa
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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