Increased Synapse Elimination by Inflammatory Cells Contributes to Long-lasting Post-Stroke Memory Dysfunction in Old...

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Post-stroke memory dysfunction is more prevalent in older individuals.
• Brain astrocytes and microglia contribute to synapse removal during stroke, impacting neurobehavioral outcomes.

Purpose of the Study:

• To investigate the association between memory dysfunction in aged mice and increased synapse removal by inflammatory cells post-stroke.
• To evaluate the therapeutic potential of activating alpha7-nicotinic acetylcholine receptors (nAchRs) in mitigating stroke-induced memory deficits.

Main Methods:

• Ischemic stroke was induced in young and old mice.
• Memory function was assessed using Y-maze and novel object recognition (NOR) tests.
• Synapse removal, neuroinflammation, and neuronal changes were analyzed; alpha7-nAchR activation was tested in a separate cohort.

Main Results:

• Old mice exhibited significant long-term memory dysfunction, larger infarct volumes, and heightened neuroinflammation compared to young mice.
• Increased synapse engulfment by microglia/macrophages and astrocytes was observed in old mice, with astrocytes playing a more prominent role.
• Activation of alpha7-nAchRs reduced synapse removal by inflammatory cells in the hippocampus.

Conclusions:

• Increased synapse removal by inflammatory cells, especially astrocytes, contributes to long-lasting memory deficits in aged mice post-stroke.
• Targeting neuroinflammation via alpha7-nAchR activation shows promise for reducing synapse loss and improving memory function after stroke.