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Updated: May 5, 2026
Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Simvastatin exerts antiamnesic effect in Aβ25-35 -injected mice
Wen-Hong Zhi1, Yan-Ying Zeng, Zi-Hong Lu
1Department of Physiology, Nanjing Medical University, Nanjing, China; Department of Geriatric Neurology, Jiangsu Province Hospital, Nanjing, China.
Aim And Methods:
Simvastatin (SV) is reported to improve cognition and slow the progression of Alzheimer's disease (AD). This study explored the mechanisms underlying the antiamnesic effect of SV in AD using behavior tests, histological examination, western blot analysis, and electrophysiological recording technique in AD model mice created by intracerebroventricular injection (i.c.v.) of Aβ25-35 .
Results:
Chronic administration of SV (40 mg/kg/day) for 11 days after Aβ25-35 -injection ameliorated the impairment of acquisition performance and probe trail test in Morris water maze task and alternation behavior in Y maze task in Aβ25-35 -mice. Aβ25-35 -induced apoptosis of hippocampal CA1 pyramidal cells and Aβ25-35 -impaired high-frequency stimulation (HFS)-dependent long-term potentiation (LTP) induction in hippocampal Schaffer collaterale-CA1 synapse were rescued by SV-treatment. SV prevented Aβ25-35 -inhibited protein kinase B (Akt) and extracellular signal-related kinase-2 (ERK2) phosphorylation, which was sensitive to α7 nicotinic acetylcholine receptor (α7nAChR) antagonist MLA. SV-induced neuroprotection was attenuated by MLA or phosphatidylinositol-3-kinase (PI3K) antagonist LY294002. SV-rescued LTP induction was blocked by α7nAChR, PI3K or MAPK/ERK kinase (MEK) antagonist. Finally, the antiamnesia of SV in Aβ25-35 -mice was attenuated by blockage of SV-induced neuroprotection or SV-rescued LTP induction.
Conclusion:
The antiamnesia of SV in Aβ25-35 -mice depends on its neuroprotection and synaptic plasticity improvement.
Insights
Simvastatin (SV) improves memory in Alzheimer
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Alzheimer's disease (AD) is characterized by cognitive decline and memory impairment.
- Simvastatin (SV) has shown potential in improving cognition and slowing AD progression.
- Understanding the mechanisms of SV's antiamnesic effects is crucial for AD treatment.
Purpose of the Study:
- To investigate the neuroprotective and synaptic plasticity mechanisms of simvastatin's (SV) antiamnesic effects in an Alzheimer's disease (AD) mouse model.
- To explore the role of the α7 nicotinic acetylcholine receptor (α7nAChR) and downstream signaling pathways in SV's therapeutic action.
Main Methods:
- Alzheimer's disease (AD) model mice were created using intracerebroventricular (i.c.v.) injection of amyloid-beta 25-35 (Aβ25-35).
- Behavioral tests (Morris water maze, Y maze), histological examination, western blot, and electrophysiology (long-term potentiation - LTP) were employed.
- Pharmacological antagonists for α7nAChR, PI3K, and MEK were used to probe signaling pathways.
Main Results:
- Simvastatin (SV) treatment ameliorated cognitive deficits in Aβ25-35-injected mice.
- SV rescued Aβ25-35-induced neuronal apoptosis and impaired hippocampal long-term potentiation (LTP).
- SV's effects involved the activation of protein kinase B (Akt) and extracellular signal-regulated kinase 2 (ERK2) via α7 nicotinic acetylcholine receptor (α7nAChR) and phosphatidylinositol-3-kinase (PI3K) pathways.
Conclusions:
- Simvastatin's (SV) antiamnesic effects in Alzheimer's disease (AD) models are mediated by neuroprotection and synaptic plasticity enhancement.
- The α7 nicotinic acetylcholine receptor (α7nAChR) and downstream Akt/ERK signaling pathways are critical for SV's therapeutic action.
