Hydrogen Sulfide Prevents Synaptic Plasticity from VD-Induced Damage via Akt/GSK-3β Pathway and Notch Signaling...

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Vascular dementia (VD) causes neuronal injury, with mechanisms poorly understood.
• Previous studies show hydrogen sulfide (H2S) attenuates VD-induced neuronal injury.
• The neuroprotective mechanisms of H2S, particularly concerning synaptic plasticity, require further investigation.

Purpose of the Study:

• To investigate if H2S neuroprotection against VD is linked to synaptic plasticity.
• To elucidate the underlying molecular mechanisms, including the Akt/GSK-3β and Notch signaling pathways.

Main Methods:

• Adult male Wistar rats underwent bilateral common carotid artery ligation to induce VD.
• Rats received intraperitoneal sodium hydrosulfide (NaHS), an H2S donor, or saline for 3 weeks.
• Cognitive function was assessed using the Morris water maze; synaptic plasticity markers and signaling pathways were analyzed.

Main Results:

• NaHS treatment significantly reduced glutamate levels and ameliorated cognitive deficits in VD rats.
• NaHS improved long-term depression (LTD) and increased N-methyl-D-aspartate receptor subunit 2A (NMDAR 2A) expression.
• NaHS modulated the Akt/GSK-3β pathway, maintained GSK-3β activity, and activated the Notch signaling pathway (Jagged-1, Hes-1).

Conclusions:

• H2S, via NaHS, confers neuroprotection against VD by preserving synaptic plasticity.
• The protective effects are partly mediated through the Akt/GSK-3β and Notch signaling pathways.
• H2S modulates NMDAR 2A/2B ratio, enhancing synaptic plasticity in VD models.