R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

Shanmugasundaram, Bharanidharan; Aher, Yogesh D.; Aradská, Jana; Ilić, Marija; Feyissa, Daniel Daba; Kalaba, Predrag; Aher, Nilima Y.; Dragačević, Vladimir; Marouf, Babak Saber; Langer, Thierry; Sitte, Harald H.; Hoeger, Harald; Lubec, Jana; Korz, Volker

doi:10.1371/journal.pone.0179675

Cited by 13 publications

(12 citation statements)

References 55 publications

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“…The protein samples were separated by electrophoresis in 10% SDS-PAGE gel and transferred to PVDF membranes (GE Healthcare). The western blot procedure was performed as described previously ( Shanmugasundaram et al, 2017 ) with minor modifications. Briefly, the membrane was blocked for 1 h in 5% non-fat milk, 1x TBS, 0.05% Tween-20 and probed with the corresponding primary and secondary antibodies.…”

Section: Methodsmentioning

confidence: 99%

Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

Šmidák

Sialana

Kristofova

et al. 2017

Front. Aging Neurosci.

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Fragile X mental retardation protein (FMRP) encoded by Fragile X mental retardation 1 (FMR1) gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing of FMR1 gene expression leads to the development of Fragile X syndrome (FXS) that is characterized by intellectual disability and other behavioral problems including autism. In the rat FXS model, the lack of FMRP caused a deficit in hippocampal-dependent memory. However, the hippocampal changes of FMRP in aging rats are not fully elucidated. The current study addresses the changes in FMRP levels in dentate gyrus (DG) from young (17 weeks) and aging (22 months) Sprague – Dawley rats. The aging animal group showed significant decline in spatial reference memory. Protein samples from five rats per each group were analyzed by quantitative proteomic analysis resulting in 153 significantly changed proteins. FMRP showed significant reduction in aging animals which was confirmed by immunoblotting and immunofluorescence microscopy. Furthermore, bioinformatic analysis of the differential protein dataset revealed several functionally related protein groups with individual interactions with FMRP. These include high representation of the RNA translation and processing machinery connected to FMRP and other RNA-binding regulators including CAPRIN1, the members of Pumilio (PUM) and CUG-BP, Elav-like (CELF) family, and YTH N(6)-methyladenosine RNA-binding proteins (YTHDF). The results of the current study point to the important role of FMRP and regulation of RNA processing in the rat DG and memory decline during the aging process.

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Section: Methodsmentioning

confidence: 99%

Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

Šmidák

Sialana

Kristofova

et al. 2017

Front. Aging Neurosci.

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“…R-modafinil, (R)-2-(benzhydrylsulfinyl)acetamide was also synthesized in house as reported previously [35] via a procedure based on the US 7,812,193 B2 patent application.…”

Section: Drugs and Treatmentsmentioning

confidence: 99%

Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (S)-CE-123 on Mesocorticolimbic Dopamine System

et al. 2020

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Treatments for cognitive impairments associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder or narcolepsy, aim at modulating extracellular dopamine levels in the brain. CE-123 (5-((benzhydrylsulfinyl)methyl) thiazole) is a novel modafinil analog with improved specificity and efficacy for dopamine transporter inhibition that improves cognitive and motivational processes in experimental animals. We studied the neuropharmacological and behavioral effects of the S-enantiomer of CE-123 ((S)-CE-123) and R-modafinil in cognitive- and reward-related brain areas of adult male rats. In vivo single unit recordings in anesthetized animals showed that (S)-CE-123, but not R-modafinil, dose-dependently (1.25 to 10 mg/kg i.v.) reduced firing of pyramidal neurons in the infralimbic/prelimbic (IL/PrL) cortex. Neither compound the affected firing activity of ventral tegmental area dopamine cells. In freely moving animals, (S)-CE-123 (10 mg/kg i.p.) increased extracellular dopamine levels in the IL/PrL, with different patterns when compared to R-modafinil (10 mg/kg i.p.); in the nucleus accumbens shell, a low and transitory increase of dopamine was observed only after (S)-CE-123. Neither (S)-CE-123 nor R-modafinil initiated the emission of 50-kHz ultrasonic vocalizations, a behavioral marker of positive affect and drug-mediated reward. Our data support previous reports of the procognitive effects of (S)-CE-123, and show a minor impact on reward-related dopaminergic areas.

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“…In agreement with our study, Shanmugasundaram et al . showed that DMSO (same as our dosage) impairs spatial memory and decreases synaptic plasticity [ 27 ]. Also, Budinich et al .…”

Section: Discussionmentioning

confidence: 99%

Concurrent Effects of Exercise and Curcumin on Spatial Learning and Memory in Sensitized Male Mice Following Morphine Administration

Elhampour

Azarbayjani

Nasehi

et al. 2019

GMJ

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Background: Exercise and Curcumin have positive effects on spatial memory and cognition independently. The present study aims to investigate whether the combination of ineffectual dosage of these factors can affect cognition and as a solvent if DMSO is involved in Curcumin effects. Materials and Methods: Male NMRI mice (1-month-old) swam (1 week) for 60 minutes (5days/week) and injected with morphine (2.5 mg/ml/kg, intraperitoneal) for five days. Spatial learning and memory were assessed by Moris Water Maze test on the 10th day after stopping morphine injection. Results: The findings revealed that exercise, dimethyl sulfoxide (DMSO), and Curcumin increased memory formation induced by 2.5 mg/ml/kg morphine. DM-SO+exercise decreased memory formation induced by morphine, but curcumin +exercise could return the effect of DMSO on the cognition. Conclusion: As a solvent, DMSO had independent effects on memory, which lead to memory impairment in combination with exercise. Therefore, considering its unpredictable effects on cognitive performance, it should be replaced with another solvent or might be used carefully in behavioral experiments. [GMJ.2019;8:e1072]

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R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

Cited by 13 publications

References 55 publications

Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

Reduced Levels of the Synaptic Functional Regulator FMRP in Dentate Gyrus of the Aging Sprague-Dawley Rat

Neurophysiological and Neurochemical Effects of the Putative Cognitive Enhancer (S)-CE-123 on Mesocorticolimbic Dopamine System

Concurrent Effects of Exercise and Curcumin on Spatial Learning and Memory in Sensitized Male Mice Following Morphine Administration

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