255. Unveiling the Cognitive Enhancing Effects of Rs-d7, a Novel Ndmar Modulator, on Hippocampus-dependent Learning and Memory in Mice
Year: 2025
Type: article
Abstract: Background Excitatory neurotransmission mediated by the N-methyl-D-aspartate receptor (NMDAR) is a key glutamate receptor in the mammalian central nervous system. Over recent decades, significant progress has been made in understanding NMDARs as pivotal contributors to cognitive processes such as learning, memory, and spatial navigation. Disruption of NMDAR signaling can lead to cognitive deficits in both human and animal models. Conversely, compounds that enhance NMDAR function hold promise for improving cognitive performance. RS-D7, a novel modulator of NMDARs, acts as a D-amino acid oxidase (DAO) inhibitor, potentially boosting NMDAR-mediated signaling and enhancing cognitive function. Aims & Objectives Based on its pharmacological profile, RS-D7 is hypothesized to enhance cognitive function by modulating NMDAR activity. This study aims to explore the cognitive-enhancing effects of RS-D7 on hippocampus-dependent spatial learning and memory in mice. The specific objectives are as follows: (1) to assess the acute functional impact of RS-D7, (2) to investigate its potential to enhance spatial learning and memory, and (3) to examine neuromorphological changes in hippocampal CA1 pyramidal neurons following RS-D7 treatment. Method Adult male C57BL/6 mice were used in this study. In Experiment 1, the acute effects of RS-D7 (40 mg/kg, i.p.) on long-term potentiation (LTP) were examined in hippocampal slices. In Experiment 2, spatial learning and memory were assessed using the Morris Water Maze (MWM; 120 cm diameter) over 11 days, with daily injections of RS-D7 (40 mg/kg, i.p.) or vehicle administered 20 minutes before each training session. Search strategy analyses were performed during the MWM to evaluate allocentric memory. In Experiment 3, Golgi-Cox staining was employed to measure dendritic spine density in hippocampal CA1 pyramidal neurons following the 11 days of MWM training. Results In Experiment 1, RS-D7 treatment significantly enhanced hippocampal LTP compared to controls. In Experiment 2, RS-D7-treated mice exhibited notable improvements in both the training phase and the probe test of the MWM. These mice also showed a stronger preference for allocentric navigation strategies, suggesting enhanced spatial memory. In Experiment 3, RS-D7 treatment resulted in a remarkable increase in dendritic spine density in hippocampal CA1 pyramidal neurons following 11 days of MWM training. Discussion & Conclusions Our findings suggest that RS-D7 enhances hippocampus-dependent spatial learning and memory in mice. Electrophysiological data, which confirm improved synaptic function, along with neuromorphological changes in CA1 neurons, further support the observed behavioral enhancements. Ongoing data collection is expected to provide deeper insights into the underlying mechanisms by which RS-D7 modulates neurocognitive functions. Collectively, these results suggest that RS-D7 has potential as both a cognitive enhancer and a therapeutic candidate for treating cognitive deficits in neuropsychiatric disorders, opening new avenues for treatment.
Authors: H-C Chien, D-Z Luo, Y-C Shih, W-S Lai
Institution: National Taiwan University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,693
OpenAlex ID: W4413285151