Activating Transcription Factor 3 Diminishes Ischemic Cerebral Infarct and Behavioral Deficit by Downregulating...

Area of Science:

• Neuroscience
• Molecular Biology
• Ischemic Stroke Research

Background:

• Activating transcription factor 3 (ATF3) is a stress-induced factor and neuronal injury marker.
• In vitro studies suggest ATF3 protects neurons by suppressing CTMP and activating Akt/PKB.
• The in vivo relevance of this neuroprotective pathway in ischemic stroke is unknown.

Purpose of the Study:

• To investigate the role of the ATF3→CTMP pathway in the ischemic brain in vivo.
• To determine if ATF3 exhibits neuroprotective effects against ischemic insult.
• To explore the therapeutic potential of modulating ATF3 and CTMP levels for stroke treatment.

Main Methods:

• Utilized a middle cerebral artery (MCA) occlusion model in mice.
• Employed gain-of-function (Ad-ATF3) and loss-of-function (ATF3 knockout) approaches.
• Investigated gene and protein expression levels (ATF3, CTMP, p-Akt).
• Used siRNA knockdown of CTMP to assess its impact.

Main Results:

• ATF3 mRNA was rapidly induced during ischemia-reperfusion.
• ATF3 overexpression reduced infarct size and improved neurological deficits.
• ATF3 knockout mice exhibited larger infarcts and worse outcomes.
• ATF3 modulated CTMP and p-Akt levels, with CTMP knockdown improving outcomes.
• Results support an ATF3→CTMP neuroprotective signaling cascade.

Conclusions:

• The ATF3→CTMP signaling pathway is neuroprotective in the ischemic brain in vivo.
• ATF3 activation mitigates ischemic brain injury.
• Modulating ATF3 and CTMP represents a potential therapeutic strategy for stroke.