Object's details: Simvastatin Treatment Highlights a New Role for the Isoprenoid/Cholesterol Biosynthetic Pathway in the Modulation of Emotional Reactivity and Cognitive Performance in Rats.

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
Simvastatin Treatment Highlights a New Role for the Isoprenoid/Cholesterol Biosynthetic Pathway in the Modulation of Emotional Reactivity and Cognitive Performance in Rats.
Creator:
Segatto, Marco;
Manduca, Antonia;
Lecis, Claudio;
Rosso, Pamela;
Jóźwiak, Adam;
Swiezewska, Ewa;
Moreno, Sandra;
Trezza, Viviana;
Pallottini, Valentina
Description:
The aim of the present work was to shed light on the role played by the isoprenoid/cholesterol biosynthetic pathway in the modulation of emotional reactivity and memory consolidation in rodents through the inhibition of the key and rate-limiting enzyme 3-hydroxy 3-methylglutaryl Coenzyme A reductase (HMGR) both in vivo and in vitro with simvastatin. Three-month-old male Wistar rats treated for 21 days with simvastatin or vehicle were tested in the social interaction, elevated plus-maze, and inhibitory avoidance tasks; after behavioral testing, the amygdala, hippocampus, prefrontal cortex, dorsal and ventral striatum were dissected out for biochemical assays. In order to delve deeper into the molecular mechanisms underlying the observed effects, primary rat hippocampal neurons were used. Our results show that HMGR inhibition by simvastatin induces anxiogenic-like effects in the social interaction but not in the elevated plus maze test, and improves memory consolidation in the inhibitory avoidance task. These effects are accompanied by imbalances in the activity of specific prenylated proteins, Rab3 and RhoA, involved in neurotransmitter release and synaptic plasticity, respectively. Taken together, the present findings indicate that the isoprenoid/cholesterol biosynthetic pathway is critically involved in the physiological modulation of both emotional and cognitive processes in rodents.Neuropsychopharmacology accepted article preview online, 10 October 2013. doi:10.1038/npp.2013.284.
Object availability:
free access
Date:
2014.10.10
Type:
Article;
PeerReviewed
Language:
English
Format:
application/pdf
Relation: http://eprints.ibb.waw.pl/576 ;http://www.nature.com/npp/journal/v39/n4/full/npp2013284a.html
Subject:
RB Pathology;
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry;
RM Therapeutics. Pharmacology
Identifier: http://eprints.ibb.waw.pl/576/1/npp1.pdf ;
Segatto, Marco and Manduca, Antonia and Lecis, Claudio and Rosso, Pamela and Jóźwiak, Adam and Swiezewska, Ewa and Moreno, Sandra and Trezza, Viviana and Pallottini, Valentina (2014) Simvastatin Treatment Highlights a New Role for the Isoprenoid/Cholesterol Biosynthetic Pathway in the Modulation of Emotional Reactivity and Cognitive Performance in Rats. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 39 (4). pp. 841-854. ISSN 1740-634X
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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Object's details: Simvastatin Treatment Highlights a New Role for the Isoprenoid/Cholesterol Biosynthetic Pathway in the Modulation of Emotional Reactivity and Cognitive Performance in Rats.

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