GluN2B-specific NMDAR positive allosteric modulation reverses cognitive and behavioral abnormalities in Mecp2 and Disc1 transgenic mice
Data files
Jan 02, 2026 version files 63.53 KB
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Data_S1.xlsx
61.89 KB
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README.md
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Abstract
The GluN2B subunit of N-methyl-D-aspartate receptors (NMDAR) plays a central role in synaptic development and plasticity, and its hypofunction is linked to autism spectrum disorder, severe neurodevelopmental delay, and other neuropsychiatric diseases. Therefore, enhancing the function of this NMDAR subunit may provide an effective therapeutic strategy for correcting synaptic and behavioral deficits associated with GluN2B-hypofunction. Here, we developed a class of GluN2B-selective positive allosteric modulators and characterized the pharmacological properties and binding site of the lead compound, 175. Systemic application of 175 facilitates hippocampal long-term depression in rats. Importantly, 175 restores performances in open-field exploration and three-chamber test in Mecp2 overexpression mice. Treatment with 175 also reverses behavioral abnormalities in open-field, Y-maze spontaneous alternation, three-chamber test, and pre-pulse inhibition in Disc1 mutant mice. Our findings introduce a pharmacological tool for selectively potentiating GluN2B-NMDARs function and highlight its therapeutic potential for cognitive and behavioral symptoms associated with GluN2B hypofunction.
The file “Data S1” contains raw data underlying Figures 1–6 from the study:
GluN2B-specific NMDAR positive allosteric modulation reverses cognitive and behavioral abnormalities in Mecp2 and Disc1 transgenic mice
Please refer to the corresponding figures and figure legends in the published article for detailed information on data units, experimental conditions, and analysis methods.
Description of the data and file structure
Fig. 1, Data unit: normalized response. Entries labeled as n/a indicate missing values corresponding to conditions that were not measured in the dose–response experiments.
Fig. 2, Data unit: normalized response.
Fig. 3, Data unit: normalized response.
Fig. 4, Data unit: normalized response in percentage. Entries labeled as n/a indicate data points that were not collected during the induction phase of long-term depression.
Fig. 5C, Data unit: meters
Fig. 5D, Data unit: %
Fig. 5E, Data unit: meters
Fig. 5F, Data unit: %
Fig. 5H, Data unit: seconds
Fig. 5I, Data unit: index from -1 to 1
Fig. 5K, Data unit: seconds
Fig. 5L, Data unit: index from -1 to 1
Fig. 6C, Data unit: meters
Fig. 6D, Data unit: seconds
Fig. 6E, Data unit: meters
Fig. 6F, Data unit: seconds
Fig. 6H, Data unit: %
Fig. 6I, Data unit: number of entries
Fig. 6J, Data unit: %
Fig. 6K, Data unit: number of entries
Fig. 6M, Data unit: index from -1 to 1
Fig. 6N, Data unit: index from -1 to 1
Fig. 6P, Data unit: startle amplitude
Fig. 6Q, Data unit: %
Fig. 6R, Data unit: %
Fig. 6S, Data unit: %