High dose simvastatin and rosuvastatin impair cognitive abilities of healthy rats via decreasing hippocampal neurotrophins and irisin
•High dose simvastatin (SMV) and rosuvastatin (RSV) decreased locomotor activity.•High dose SMV and RSV impaired anxiety, learning and memory.•High dose SMV and RSV decreased hippocampal neurotropins and irisin.•High dose SMV and RSV increased irisin and BDNF in the skeletal muscle. Statins are chol...
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| Published in | Brain research bulletin Vol. 165; pp. 81 - 89 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.12.2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0361-9230 1873-2747 1873-2747 |
| DOI | 10.1016/j.brainresbull.2020.09.019 |
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| Abstract | •High dose simvastatin (SMV) and rosuvastatin (RSV) decreased locomotor activity.•High dose SMV and RSV impaired anxiety, learning and memory.•High dose SMV and RSV decreased hippocampal neurotropins and irisin.•High dose SMV and RSV increased irisin and BDNF in the skeletal muscle.
Statins are cholesterol lowering drugs that decrease the risk of cardiovascular events, but they are related with a few unfavorable symptoms in skeletal muscle including myopathy, and mild to moderate fatigue. Additionally, there has been discrepancies about the impacts of statins on brain and cognition. This study aimed to examine the impacts of two different statins, lipophilic simvastatin and hydrophilic rosuvastatin on cognitive functions in normal healthy rats. Simultaneously, we investigated the alterations of neurotropins and irisin levels in hippocampus and myokine levels in skeletal muscle.
The rats were dosed with 88 mg kg body weight−1 day−1 simvastatin (n = 8), 150 mg kg body weight−1 day−1 rosuvastatin (n = 8) or vehicle (n = 8) for 18 days via oral gavage. After that behavioral assessment was performed and hippocampus and skeletal muscle samples were taken for the analysis of neurotrophins and irisin levels.
Locomotion and learning and memory functions were lower, but anxiety levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05). Hippocampal neurotrophins and irisin levels were lower, but skeletal muscle brain-derived neurotrophic factor (BDNF) and irisin levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05).
These findings suggest that high dose simvastatin and rosuvastatin impair cognitive functions via decreasing BDNF, NGF and irisin levels in the hippocampus. |
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| AbstractList | •High dose simvastatin (SMV) and rosuvastatin (RSV) decreased locomotor activity.•High dose SMV and RSV impaired anxiety, learning and memory.•High dose SMV and RSV decreased hippocampal neurotropins and irisin.•High dose SMV and RSV increased irisin and BDNF in the skeletal muscle.
Statins are cholesterol lowering drugs that decrease the risk of cardiovascular events, but they are related with a few unfavorable symptoms in skeletal muscle including myopathy, and mild to moderate fatigue. Additionally, there has been discrepancies about the impacts of statins on brain and cognition. This study aimed to examine the impacts of two different statins, lipophilic simvastatin and hydrophilic rosuvastatin on cognitive functions in normal healthy rats. Simultaneously, we investigated the alterations of neurotropins and irisin levels in hippocampus and myokine levels in skeletal muscle.
The rats were dosed with 88 mg kg body weight−1 day−1 simvastatin (n = 8), 150 mg kg body weight−1 day−1 rosuvastatin (n = 8) or vehicle (n = 8) for 18 days via oral gavage. After that behavioral assessment was performed and hippocampus and skeletal muscle samples were taken for the analysis of neurotrophins and irisin levels.
Locomotion and learning and memory functions were lower, but anxiety levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05). Hippocampal neurotrophins and irisin levels were lower, but skeletal muscle brain-derived neurotrophic factor (BDNF) and irisin levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05).
These findings suggest that high dose simvastatin and rosuvastatin impair cognitive functions via decreasing BDNF, NGF and irisin levels in the hippocampus. Statins are cholesterol lowering drugs that decrease the risk of cardiovascular events, but they are related with a few unfavorable symptoms in skeletal muscle including myopathy, and mild to moderate fatigue. Additionally, there has been discrepancies about the impacts of statins on brain and cognition. This study aimed to examine the impacts of two different statins, lipophilic simvastatin and hydrophilic rosuvastatin on cognitive functions in normal healthy rats. Simultaneously, we investigated the alterations of neurotropins and irisin levels in hippocampus and myokine levels in skeletal muscle.BACKGROUNDStatins are cholesterol lowering drugs that decrease the risk of cardiovascular events, but they are related with a few unfavorable symptoms in skeletal muscle including myopathy, and mild to moderate fatigue. Additionally, there has been discrepancies about the impacts of statins on brain and cognition. This study aimed to examine the impacts of two different statins, lipophilic simvastatin and hydrophilic rosuvastatin on cognitive functions in normal healthy rats. Simultaneously, we investigated the alterations of neurotropins and irisin levels in hippocampus and myokine levels in skeletal muscle.The rats were dosed with 88 mg kg body weight-1 day-1 simvastatin (n = 8), 150 mg kg body weight-1 day-1 rosuvastatin (n = 8) or vehicle (n = 8) for 18 days via oral gavage. After that behavioral assessment was performed and hippocampus and skeletal muscle samples were taken for the analysis of neurotrophins and irisin levels.METHODSThe rats were dosed with 88 mg kg body weight-1 day-1 simvastatin (n = 8), 150 mg kg body weight-1 day-1 rosuvastatin (n = 8) or vehicle (n = 8) for 18 days via oral gavage. After that behavioral assessment was performed and hippocampus and skeletal muscle samples were taken for the analysis of neurotrophins and irisin levels.Locomotion and learning and memory functions were lower, but anxiety levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05). Hippocampal neurotrophins and irisin levels were lower, but skeletal muscle brain-derived neurotrophic factor (BDNF) and irisin levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05).RESULTSLocomotion and learning and memory functions were lower, but anxiety levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05). Hippocampal neurotrophins and irisin levels were lower, but skeletal muscle brain-derived neurotrophic factor (BDNF) and irisin levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05).These findings suggest that high dose simvastatin and rosuvastatin impair cognitive functions via decreasing BDNF, NGF and irisin levels in the hippocampus.CONCLUSIONThese findings suggest that high dose simvastatin and rosuvastatin impair cognitive functions via decreasing BDNF, NGF and irisin levels in the hippocampus. Statins are cholesterol lowering drugs that decrease the risk of cardiovascular events, but they are related with a few unfavorable symptoms in skeletal muscle including myopathy, and mild to moderate fatigue. Additionally, there has been discrepancies about the impacts of statins on brain and cognition. This study aimed to examine the impacts of two different statins, lipophilic simvastatin and hydrophilic rosuvastatin on cognitive functions in normal healthy rats. Simultaneously, we investigated the alterations of neurotropins and irisin levels in hippocampus and myokine levels in skeletal muscle. The rats were dosed with 88 mg kg body weight day simvastatin (n = 8), 150 mg kg body weight day rosuvastatin (n = 8) or vehicle (n = 8) for 18 days via oral gavage. After that behavioral assessment was performed and hippocampus and skeletal muscle samples were taken for the analysis of neurotrophins and irisin levels. Locomotion and learning and memory functions were lower, but anxiety levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05). Hippocampal neurotrophins and irisin levels were lower, but skeletal muscle brain-derived neurotrophic factor (BDNF) and irisin levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05). These findings suggest that high dose simvastatin and rosuvastatin impair cognitive functions via decreasing BDNF, NGF and irisin levels in the hippocampus. |
| Author | Belviranli, Muaz Okudan, Nilsel |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33010350$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1007_s10787_023_01240_x crossref_primary_10_1177_02698811211060307 crossref_primary_10_1002_jbmr_4269 crossref_primary_10_3389_fpsyt_2021_702617 crossref_primary_10_1002_med_21875 crossref_primary_10_3390_jpm12121981 crossref_primary_10_1038_s41398_023_02533_z crossref_primary_10_3389_fnagi_2022_968039 crossref_primary_10_1016_j_neuroscience_2024_05_012 crossref_primary_10_1016_j_toxrep_2025_101958 |
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| Keywords | Irisin Rosuvastatin Cognition Anxiety Neurotrophins Simvastatin |
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| Title | High dose simvastatin and rosuvastatin impair cognitive abilities of healthy rats via decreasing hippocampal neurotrophins and irisin |
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