Long-term atorvastatin treatment leads to alterations in behavior, cognition, and hippocampal biochemistry

Autor: Ingrid R. Niesman, David M. Roth, Victoria B. Risbrough, Weihua Cui, Alice E. Zemljic-Harpf, Brian P. Head, Hemal H. Patel, Jan M. Schilling, Piyush M. Patel, John C. Drummond, Joseph C. Godoy
Rok vydání: 2014
Předmět:
Reflex
Startle
Startle response
Aging
Time Factors
Atorvastatin
Syntaxin 1
Pharmacology
Neurodegenerative
Inbred C57BL
Alzheimer's Disease
Hippocampus
Medical and Health Sciences
Behavioral Neuroscience
chemistry.chemical_compound
Mice
Cognition
Lipid raft
Behavior
Animal
medicine.diagnostic_test
biology
Startle
Brain
Lipid
Cholesterol
Mental Health
Biochemistry
Neurological
lipids (amino acids
peptides
and proteins)
Mevalonate pathway
Disks Large Homolog 4 Protein
medicine.drug
medicine.medical_specialty
Hypercholesterolemia
Synaptophysin
Motor Activity
Article
Internal medicine
Reflex
Behavioral and Social Science
medicine
Acquired Cognitive Impairment
Animals
Pyrroles
Maze Learning
Behavior
Neurology & Neurosurgery
Animal
Psychology and Cognitive Sciences
Neurosciences
Membrane Proteins
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Barnes maze
Brain Disorders
Mice
Inbred C57BL
Endocrinology
Membrane protein
chemistry
Heptanoic Acids
biology.protein
Exploratory Behavior
Dementia
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Guanylate Kinases
Popis: Membrane/lipid rafts (MLR) are plasmalemmal microdomains that are essential for neuronal signaling and synaptic development/stabilization. Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the biosynthesis of mevalonic, a precursor to cholesterol via the mevalonate pathway. Because there has been controversy over the effects of statins on neuronal and cognitive function, we investigated the impact of long-term atorvastatin treatment (5mg/kg/d for 7 months by oral gavage) on behavior, cognition, and brain biochemistry in mice. We hypothesized that long-term statin treatment would alter lipid rafts and cognitive function. Atorvastatin treatment resulted in behavioral deficits as measured in paradigms for basic exploration (open field activity) and cognitive function (Barnes maze, startle response) without impairment in global motor function (Rotor Rod). Furthermore, significant changes in MLR-associated proteins (syntaxin-1α and synaptophysin) and a global change of post-synaptic density protein-95 (PSD95) were observed. The observed decreases in the MLR-localized pre-synaptic vesicle proteins syntaxin-1α and synaptophysin suggest a molecular mechanism for the statin-associated impairment of cognitive function that was observed and that has been suggested by the clinical literature.
Databáze: OpenAIRE
Externí odkaz: