iTRAQ-based proteomics analysis of hippocampus in spatial memory deficiency rats induced by simulated microgravity

Area of Science:

• Neuroscience
• Space Biology
• Proteomics

Background:

• Spaceflight poses risks to astronaut cognitive function, crucial for mission success.
• Simulated microgravity (SM) is a significant environmental risk factor during spaceflight.
• Understanding the mechanisms of microgravity-induced cognitive impairment is vital for developing countermeasures.

Purpose of the Study:

• To investigate the effects of 28-day SM on hippocampus-dependent learning and memory in rats.
• To elucidate the underlying molecular mechanisms of SM-induced cognitive dysfunction.
• To identify potential therapeutic targets for mitigating cognitive impairments in astronauts.

Main Methods:

• Tail-suspension model (30°) in rats to simulate microgravity for 28 days.
• Behavioral testing using the Morris water maze (MWM) to assess learning and memory.
• iTRAQ-based proteomics to analyze hippocampal protein expression.
• Western blot verification and neurotransmitter concentration analysis.

Main Results:

• 28-day SM exposure significantly impaired spatial learning and memory in the MWM test.
• Proteomic analysis identified 147 differentially expressed proteins in the hippocampus.
• Elevated expression of glutamate receptors (GluR1, GluR4) and increased glutamic acid (Glu) were observed.
• Decreased concentrations of serotonin (5-HT), dopamine (DA), GABA, and epinephrine (E) were detected.

Conclusions:

• Long-term SM exposure degrades spatial learning and memory capabilities.
• Mechanisms may involve glutamate excitotoxicity and neurotransmitter imbalances in the hippocampus.
• Findings provide insights for countermeasures against cognitive impairment during spaceflight.