Microcystin-LR inhibited hippocampal long-term potential via regulation of the glycogen synthase kinase-3β pathway

Area of Science:

• Neuroscience
• Toxicology
• Cellular Biology

Background:

• Cyanobacteria-derived microcystin-LR (MCLR) is known to cause cognitive dysfunction.
• The precise molecular mechanisms underlying MCLR-induced cognitive impairment remain unclear.
• Long-term potentiation (LTP) in the hippocampus is crucial for learning and memory.

Purpose of the Study:

• To investigate the role of MCLR in hippocampal long-term potentiation (LTP) in the dentate gyrus (DG).
• To elucidate the involvement of glycogen synthase kinase-3β (GSK-3β) in MCLR-induced cognitive deficits.

Main Methods:

• In vivo electrophysiological recordings in rat hippocampus to assess LTP.
• Western blotting to analyze the phosphorylation levels of GSK-3β.
• Intracerebroventricular (ICV) administration of MCLR and GSK-3β inhibitors (LiCl, SB216763).
• Measurement of protein phosphatase (PP) activity in brain tissue.

Main Results:

• MCLR suppressed the induction of LTP in the rat hippocampus.
• Simultaneous inhibition of GSK-3β with LiCl or SB216763 attenuated MCLR-induced LTP impairments.
• ICV injection of MCLR led to decreased phosphorylation of GSK-3β at Ser9, indicating its activation.
• MCLR administration stimulated protein phosphatase activity, potentially activating GSK-3β through dephosphorylation.

Conclusions:

• GSK-3β plays a critical role in mediating cognitive deficits induced by microcystin-LR.
• MCLR-induced cognitive impairment involves the activation of GSK-3β, possibly through enhanced protein phosphatase activity.