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Simvastatin Attenuates Hippocampal MMP-9 Expression in the Streptozotocin-Induced Cognitive Impairment

Soheila Adeli1,2, Maryam Zahmatkesh1,2,3, Mitra Ansari Dezfouli1

  • 1Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Iranian Biomedical Journal
|September 17, 2018
PubMed
Abstract

Insights

Simvastatin treatment reduced matrix metalloproteinase-9 (MMP-9) expression in a rat model of Alzheimer's disease (AD). This reduction correlated with improved cognitive function and reduced hippocampal damage, suggesting a neuroprotective role for simvastatin in AD.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Matrix metalloproteinase-9 (MMP-9) is implicated in neurodegenerative disorders like Alzheimer's disease (AD).
  • Statins may offer neuroprotection by inhibiting MMP-9 expression.

Purpose of the Study:

  • To investigate the effect of simvastatin on hippocampal MMP-9 expression in an AD rat model.
  • To explore the correlation between MMP-9 levels and cognitive function.

Main Methods:

  • Administration of simvastatin (5 mg/kg) for three weeks in streptozotocin (STZ)-induced AD rats.
  • Assessment of spatial long-term memory using the Morris water maze (MWM) test.
  • Quantification of hippocampal MMP-9 expression via quantitative polymerase chain reaction (qPCR).

Main Results:

  • STZ-induced rats exhibited impaired learning and memory, elevated hippocampal MMP-9, and cell damage.
  • Simvastatin treatment normalized MMP-9 levels, improved spatial memory, and reduced hippocampal damage.
  • A significant negative correlation (r = 0.77) was observed between MMP-9 expression and cognitive function.

Conclusions:

  • Simvastatin exerts neuroprotective effects against cognitive impairment in AD models, partly through modulating MMP-9 expression.
  • Reduced MMP-9 expression is associated with improved cognitive function following simvastatin treatment.
  • Understanding simvastatin's mechanism offers insights for developing novel therapeutic strategies for AD.
Keywords:
Alzheimer’s diseaseMatrix metalloproteinase-9Simvastatin

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