Ligustilide Ameliorates Memory Deficiency in APP/PS1 Transgenic Mice via Restoring Mitochondrial Dysfunction

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline.
• Ligustilide (LIG), a component of Radix angelicae sinensis, has shown promise in AD models, but its mechanisms require further elucidation.
• Understanding LIG's effects on AD pathology is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the protective effects of Ligustilide (LIG) against Alzheimer's disease (AD) progression in APP/PS1 mice.
• To explore the underlying mechanisms of LIG's action, including its impact on amyloid-beta (Aβ) levels, mitochondrial function, and synaptic integrity.
• To evaluate LIG's potential as an antidementia therapeutic agent.

Main Methods:

• Administration of LIG (10 mg/kg, 40 mg/kg) daily to 7-month-old APP/PS1 mice for eight weeks.
• Behavioral testing using Morris water maze and Y-maze to assess memory deficits.
• Biochemical analyses including thioflavin-S staining, Western blotting for Aβ, APP, ADAM10, SAPPα, PreP, mitochondrial proteins (Drp1, Mfn1, Mfn2, Opa1), synaptic markers (PSD-95, synaptophysin, synapsin 1), oxidative stress markers (MDA, ROS, Mn-SOD), and ATP levels.
• Mitochondrial morphology assessment via transmission electron microscopy.

Main Results:

• LIG treatment significantly improved memory deficits in APP/PS1 mice.
• LIG reduced brain Aβ levels and ameliorated mitochondrial dysfunction, evidenced by improved ATP levels and enzyme activities (CCO, SDH).
• LIG modulated mitochondrial dynamics by altering fission/fusion protein levels, reduced oxidative stress, and protected synaptic structures.

Conclusions:

• Ligustilide (LIG) effectively ameliorates cognitive deficits in an Alzheimer's disease mouse model.
• LIG exerts neuroprotection by reducing amyloid-beta burden, restoring mitochondrial function and dynamics, and preserving synaptic integrity.
• These findings suggest LIG holds significant potential as a therapeutic agent for Alzheimer's disease.