Pressure-dependent effects of hyperbaric oxygen on hippocampal CREB-BDNF signaling and associated changes in synaptic...

Hyperbaric oxygen therapy (HBOT) has been proposed to modulate brain function, yet its pressure-dependent effects on hippocampal plasticity and cognition remain unclear. This study investigated the effects of HBOT at 1.6, 2.0, and 2.4 atmospheres absolute (ATA) on molecular pathways underlying synaptic plasticity and inhibitory neurotransmission, as well as on cognitive performance in healthy rats. Animals were exposed to HBOT for 1 h/day over 14 consecutive days. Cognitive performance was assessed using the Novel Object Recognition (NOR) and Y-maze tests. Hippocampal expression of brain-derived neurotrophic factor, cAMP response element-binding protein (CREB), phosphorylated CREB (p-CREB), parvalbumin, and glutamate decarboxylase-67 (GAD67) was analyzed by Western blotting and immunohistochemistry. mRNA levels of postsynaptic density protein-95, synapsin I, and synaptophysin were quantified by real-time PCR. HBOT significantly increased BDNF, CREB, and p-CREB expression, with maximal effects observed at 2.0 ATA. Synaptic gene expression was also significantly upregulated, indicating activation of plasticity-related transcriptional programs. Notably, parvalbumin expression was increased, whereas GAD67 levels were decreased in the 2.0 and 2.4 ATA groups, suggesting modulation of inhibitory neurotransmission and a shift toward a plasticity-permissive network state. Behavioral analysis revealed a significant improvement in NOR performance at 2.0 ATA only. In contrast, the Y-maze discrimination index showed an increasing trend in the 2.0 ATA group, but this change did not reach statistical significance. These findings indicate that HBOT exerts pressure-dependent effects on hippocampal plasticity and cognition, with 2.0 ATA representing the optimal condition for enhancing molecular and behavioral outcomes.