Tissue-type plasminogen activator protects the postsynaptic density in the ischemic brain.

Area of Science:

• Neuroscience
• Molecular Biology
• Ischemic Stroke Research

Background:

• Cerebral ischemia triggers tissue-type plasminogen activator (tPA) release.
• Postsynaptic density protein-95 (PSD-95) is crucial for synaptic function and glutamate receptor anchoring.
• PSD-95 is lost from the postsynaptic density (PSD) during early cerebral ischemia.

Purpose of the Study:

• To investigate the role of tPA in regulating PSD-95 during cerebral ischemia.
• To elucidate the mechanism by which tPA influences PSD-95 and synaptic protection.
• To determine if tPA administration can mitigate ischemic brain injury.

Main Methods:

• Investigated tPA-induced local translation of PSD-95 mRNA.
• Examined plasminogen-independent activation of TrkB receptors by tPA.
• Assessed the effect of neuronal and recombinant tPA (rtPA) on PSD-95 levels during ischemia.
• Analyzed the impact of tPA on AMPA receptor phosphorylation and recruitment.
• Evaluated TrkB-mediated protection of dendritic spines.

Main Results:

• tPA induces local translation of PSD-95 mRNA and its recruitment to the PSD via TrkB activation.
• tPA administration prevents the loss of PSD-95 from the PSD during early cerebral ischemia.
• tPA inhibits AMPA receptor phosphorylation and recruitment, reducing excitotoxicity.
• tPA promotes TrkB-mediated protection of dendritic spines against hypoxic damage.

Conclusions:

• tPA acts as a synaptic protector in the ischemic brain.
• tPA's protective effects involve preserving PSD-95 and mitigating excitotoxicity.
• Targeting tPA signaling pathways may offer therapeutic strategies for ischemic stroke.