ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Simvastatin treatment highlights a new role for the isoprenoid/cholesterol biosynthetic pathway in the modulation of emotional reactivity and cognitive performance in rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 52 citations in OpenAlex.
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- Simvastatin Significantly Reduced Alcohol-Induced Cardiac Damage in Adolescent Mice.Cardiovascular toxicology · 2024Article
- Cognitive function in dyslipidemia patients: exploring the impact of statins.Frontiers in neurology · 2024Article
- The pharmacological bases for repurposing statins in depression: a review of mechanistic studies.Translational psychiatry · 2023Review
- Simvastatin rescues memory and granule cell maturation through the Wnt/β-catenin signaling pathway in a mouse model of Alzheimer's disease.Cell death & disease · 2022Article
- Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome.International journal of molecular sciences · 2022Article
- Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus.Nutrients · 2021Article
- BETs inhibition attenuates oxidative stress and preserves muscle integrity in Duchenne muscular dystrophy.Nature communications · 2020Article
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- Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins by JQ1 Unravels a Novel Epigenetic Modulation to Control Lipid Homeostasis.International journal of molecular sciences · 2020Article
- Unidirectional opioid-cannabinoid cross-tolerance in the modulation of social play behavior in rats.Psychopharmacology · 2019Article
- Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome.International journal of molecular sciences · 2019Review
- Preliminary Study on Clusterin Protein (sCLU) Expression in PC-12 Cells Overexpressing Wild-Type and Mutated (Swedish)International journal of molecular sciences · 2019Article
- Statins and the Brain: More than Lipid Lowering Agents?Current neuropharmacology · 2019Review
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- Hippocampus ghrelin receptor signaling promotes socially-mediated learned food preference.Neuropharmacology · 2018Article
- Epigenetic targeting of bromodomain protein BRD4 counteracts cancer cachexia and prolongs survival.Nature communications · 2017Article
- Targeting anandamide metabolism rescues core and associated autistic-like symptoms in rats prenatally exposed to valproic acid.Translational psychiatry · 2016Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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