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Simvastatin Improves Behavioral Disorders and Hippocampal Inflammatory Reaction by NMDA-Mediated Anti-inflammatory
Junqiang Yan1,2, Anran Liu3, Hua Fan4
1The First Affiliated Hospital, Neurological Diseases Institute, College of Clinical Medicine of Henan University of Science and Technology, Jinghua Road 24, Luoyang, 471003, Henan, People's Republic of China. yanjq20062007@126.com.
Abstract:
The cognitive function impairment may be related to the inflammation of the hippocampus in Parkinson's disease. Simvastatin can play a positive role in Parkinson's disease. The purpose of this study was to investigate whether simvastatin could improve behavioral disorders, especially depression, anxiety and cognitive function in mouse PD models, and further explore the molecular mechanism. In the present study, C57BL-6 mice underwent intraperitoneal injection of MPTP (30 mg/kg) once a day for 5 consecutive days. At the same time, simvastatin (10 mg/kg) was pretreated for 2 days before the Parkinson's disease model was established, and then continued for 5 days, and the control group underwent intraperitoneal injection of MK801 (dizocilpine, 0.2 mg/kg) and saline solution. Depression status was tested by a tail suspension test and a sucrose splash test, followed by an open-field test and an elevated plus maze test to determine anxiety levels. Spatial behavior and muscle status were measured with a water maze and a rotarod test. The expression of RNA and protein of N-methyl-D-aspartate receptor subtype 2B (NMDAR2B), nerve growth factor IB (Nur77), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF) α were assayed by real-time polymerase chain reaction and Western blot. Our results showed that simvastatin can improve the cognitive function, anxiety, and depression of PD mice with MPTP injury. Simvastatin reversed the NMDAR2B increase, restored Nur77 downward, and reduced the expression of COX-2 and TNF-α in MPTP-treated mice. This role of simvastatin was consistent with MK801 in increasing the expression of Nur77 and inhibiting NMDAR2B and cytokines in MPTP-lesioned PD mice. These findings suggest that reversed the NMDAR2B increase, restored Nur77 downward, and reduced the expression of COX-2 and TNF-α in MPTP-treated mice may be one of the mechanisms that simvastatin improves cognitive functions, depression, and anxiety in MPTP-lesioned mice.
Insights
Simvastatin treatment improved cognitive function, anxiety, and depression in Parkinson
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Parkinson's disease (PD) is associated with cognitive impairment, potentially linked to hippocampal inflammation.
- Simvastatin has shown potential benefits in Parkinson's disease models.
Purpose of the Study:
- To investigate simvastatin's effects on behavioral disorders (depression, anxiety, cognitive function) in mouse models of PD.
- To explore the underlying molecular mechanisms of simvastatin's action in PD.
Main Methods:
- MPTP-induced Parkinson's disease model in C57BL-6 mice.
- Behavioral tests: tail suspension, sucrose splash, open-field, elevated plus maze, water maze, rotarod.
- Molecular analysis: Real-time PCR and Western blot for NMDAR2B, Nur77, COX-2, and TNF-α expression.
Main Results:
- Simvastatin significantly improved cognitive function, anxiety, and depression in MPTP-treated mice.
- Simvastatin reversed increased N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) expression.
- Simvastatin restored decreased nerve growth factor IB (Nur77) expression and reduced cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) levels.
Conclusions:
- Simvastatin ameliorates behavioral deficits in a mouse model of Parkinson's disease.
- Molecular mechanisms involve modulation of NMDAR2B, Nur77, COX-2, and TNF-α.
- These findings suggest simvastatin as a potential therapeutic agent for cognitive and mood disturbances in PD.
