Drug Development.

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Chronic Unpredictable Stress (CUS) models cognitive impairment and neurodegeneration via the kynurenine (KYN) pathway.
• Stress elevates cortisol, activating microglia, increasing quinolinic acid (QA), and reducing brain-derived neurotrophic factor (BDNF), leading to neurodegeneration.
• Avicularin, known for antioxidant and antidepressant effects, was investigated for neuroprotection against CUS-induced cognitive deficits.

Purpose of the Study:

• To evaluate the neuroprotective potential of avicularin against CUS-induced cognitive impairments in a mouse model.
• To assess avicularin's effects on stress biomarkers, neuroinflammation, oxidative stress, and cognitive performance.

Main Methods:

• Mice underwent CUS for five weeks, receiving avicularin (50, 100, 200 mg/kg) during the final weeks.
• Behavioral tests (forced swim, sucrose preference, Morris Water Maze, passive avoidance) assessed cognitive function.
• Biochemical analyses measured corticosterone, oxidative stress, neurotransmitters (serotonin, norepinephrine), inflammatory cytokines (TNF-α, IL-6, IL-1β), acetylcholinesterase (AChE), BDNF, and amyloid-beta.

Main Results:

• Avicularin significantly enhanced cognitive performance and reduced corticosterone levels and oxidative stress.
• Doses of 100 and 200 mg/kg avicularin increased serotonin, norepinephrine, and BDNF levels.
• Treatment led to decreased amyloid-beta, inflammatory cytokines, and AChE activity.

Conclusions:

• Avicularin exhibits significant neuroprotective effects against CUS-induced cognitive impairments.
• It effectively reduces neuroinflammation and enhances neurotrophic support.
• Avicularin holds potential as a therapeutic agent for stress-related cognitive dysfunction.