Titel
Cognitive profiling and proteomic analysis of the modafinil analogue S-CE-123 in experienced aged rats
Autor*in
István Gyertyán
Department of Pharmacology and Pharmacotherapy, Semmelweis University
Jana Lubec
Department of Neuroproteomics, Programme of Proteomics, Paracelsus Private Medical University
Alíz Judit Ernyey
Department of Pharmacology and Pharmacotherapy, Semmelweis University
... show all
Abstract
The lack of novel cognitive enhancer drugs in the clinic highlights the prediction problems of animal assays. The objective of the current study was to test a putative cognitive enhancer in a rodent cognitive test system with improved translational validity and clinical predictivity. Cognitive profiling was complemented with post mortem proteomic analysis. Twenty-seven male Lister Hooded rats (26 months old) having learned several cognitive tasks were subchronically treated with S-CE-123 (CE-123) in a randomized blind experiment. Rats were sacrificed after the last behavioural procedure and plasma and brains were collected. A label-free quantification approach was used to characterize proteomic changes in the synaptosomal fraction of the prefrontal cortex. CE-123 markedly enhanced motivation which resulted in superior performance in a new-to-learn operant discrimination task and in a cooperation assay of social cognition, and mildly increased impulsivity. The compound did not affect attention, spatial and motor learning. Proteomic quantification revealed 182 protein groups significantly different between treatment groups containing several proteins associated with aging and neurodegeneration. Bioinformatic analysis showed the most relevant clusters delineating synaptic vesicle recycling, synapse organisation and antioxidant activity. The cognitive profile of CE-123 mapped by the test system resembles that of modafinil in the clinic showing the translational validity of the test system. The findings of modulated synaptic systems are paralleling behavioral results and are in line with previous evidence for the role of altered synaptosomal protein groups in mechanisms of cognitive function.
Stichwort
DementiaLearning and memoryPharmacologyProteomics
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Scientific Reports
Band
11
ISSN
2045-2322
Erscheinungsdatum
2021
Publication
Springer Science and Business Media LLC
Erscheinungsdatum
2021
Zugänglichkeit
Rechte
Rechteangabe
© The Author(s) 2021
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