The Systemic Administration of Na⁺/H⁺ Exchanger-1 Inhibitor Impairs Hippocampal Learning and Memory

Disruptions in pH regulation are known to cause impairments in cognitive processes such as learning and memory, leading to various neurological disorders. Na⁺/H⁺ exchangers (NHEs), embedded in the membranes of neurons, are crucial for regulating intracellular and extracellular pH. This project aims to investigate the effect of cariporide, a potent inhibitor of NHE1, on spatial learning performance.

A total of 20 male Wistar rats weighing between 240 g and 360 g were divided randomly into two groups: control (n=10) and cariporide (n=10). The cariporide group received a dosage of 10 mg/kg of cariporide added to the drinking water of the rats for three weeks. The Morris Water Maze (MWM) test was conducted on all groups. Distance moved (DM), escape latency (EL), swimming speed (SS), mean distance to the platform (MdtP), and time spent in the target quadrant (TSTQ) of the rats were recorded using the monitoring and recording system.

The DM to find the platform and EL time did not show significant differences between the groups (p>0.05). The SS of the rats in the cariporide group significantly decreased compared to the control group on all days (p<0.05). The MdtP was statistically significantly increased in the cariporide group on the 2^nd and 4^th days.

The findings of this study indicate that systemic inhibition of NHE1 with cariporide affects hippocampal plasticity, leading to impairments in learning and memory. To elucidate its role in neurodegenerative diseases, further research should investigate cariporide's effect on hippocampal synaptic plasticity.