Journal: Brain research bulletin

Article Title: GABA B receptors regulate the neural stem cell potential of Pkd2l1 + cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway.

doi: 10.1016/j.brainresbull.2025.111217

Figure Lengend Snippet: Fig. 3. In vitro activation of GABABR enhanced the proliferative capacity of Pkd2l1þ CSF-CNs and protected against apoptosis. (A) Representative images showing that the proportion of EdU-positive (red) cells within neurospheres increased in the baclofen group. CGP52432 inhibited the proliferative capacity of Pkd2l1+ CSF-CNs. (B) The TUNEL assay revealed that the proportion of TUNEL-positive (red) cells decreased in the baclofen group, and CGP52432 increased the proportion of TUNEL-positive Pkd2l1+ CSF-CNs. (C) Quantitative analysis of EdU-positive (EdU+) Pkd2l1 + cells over the total number of Pkd2l1 + cells. (D) Quantification of TUNEL + Pkd2l1+ cells over the total number of Pkd2l1+ cells. * ** * P < 0.0001. Scale bar: 50 μm. (E) Western blot analysis showing the levels of the apoptosis markers cleaved caspase3 and caspase3 after baclofen treatment.

Article Snippet: Baclofen (10 μM, MedChemExpress, Shanghai, China, Cat#HY-B007) and CGP52432 (42 μM, MedChemExpress, Shanghai, China, Cat#HY-103531) were dissolved in PBS and introduced into fresh serum-free neural culture medium, which served as controls for the GABABR agonists and antagonists.

Techniques: In Vitro, Activation Assay, TUNEL Assay, Western Blot

Journal: Brain research bulletin

Article Title: GABA B receptors regulate the neural stem cell potential of Pkd2l1 + cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway.

doi: 10.1016/j.brainresbull.2025.111217

Figure Lengend Snippet: Fig. 5. The activation of GABABR in vivo mitigated the loss of spinal cord axonal myelin and axonal damage. (A) LFB staining shows the proportion of myelin area within the analyzed tissue samples in the Sham group, SCI group, SCI+PBS group, SCI+baclofen group, and SCI+CGP52432 group. (C) Immunofluorescence staining showing the proportion of cells coexpressing NF-200 (red) and Pkd2l1 (green) in the examined samples in the Sham group, SCI group, SCI+PBS group, SCI+baclofen group, and SCI+CGP524 group. (C) Quantitative analysis of LFB staining. (D) Quantification of NF-200+ Pkd2l1 + cells over the total number of Pkd2l1 + cells. * * P < 0.01, * ** P < 0.001, * ** * P < 0.0001. Scale bar: 50 μm.

Article Snippet: Baclofen (10 μM, MedChemExpress, Shanghai, China, Cat#HY-B007) and CGP52432 (42 μM, MedChemExpress, Shanghai, China, Cat#HY-103531) were dissolved in PBS and introduced into fresh serum-free neural culture medium, which served as controls for the GABABR agonists and antagonists.

Techniques: Activation Assay, In Vivo, Staining, Immunofluorescence

Journal: Brain research bulletin

Article Title: GABA B receptors regulate the neural stem cell potential of Pkd2l1 + cerebrospinal fluid-contacting neurons via the PI3K/Akt signaling pathway.

doi: 10.1016/j.brainresbull.2025.111217

Figure Lengend Snippet: Fig. 6. In vivo stimulation with GABABR enhances motor recovery in mice. (A) The BMS scoring system was used at various time intervals to assess the restoration of motor function in the Sham group, SCI group, SCI+PBS group, SCI+baclofen group, and SCI+CGP52432 group. Baclofen positively influenced the functional recovery of mice with SCI, whereas CGP52432 was associated with diminished hindfoot motor activity. (B) A schematic depiction of the hind limbs of the mice in the groups above is presented. (C) Footprint test results from the Sham group, SCI group, SCI+baclofen group, and SCI+CGP52432 group are reported on d 35 after SCI. (D) Quantitative analysis of stride length and stride width was conducted on d 35 post-SCI for the Sham group, SCI group, SCI+baclofen group, and SCI+CGP52432 group. *P < 0.05, * * P < 0.01, * ** P < 0.001, * ** * P < 0.0001.

Article Snippet: Baclofen (10 μM, MedChemExpress, Shanghai, China, Cat#HY-B007) and CGP52432 (42 μM, MedChemExpress, Shanghai, China, Cat#HY-103531) were dissolved in PBS and introduced into fresh serum-free neural culture medium, which served as controls for the GABABR agonists and antagonists.

Techniques: In Vivo, Functional Assay, Activity Assay

Journal: Cell Research

Article Title: Cryo-EM structures of inactive and active GABA B receptor

doi: 10.1038/s41422-020-0350-5

Figure Lengend Snippet: a, b Cryo-EM density maps (left), models (middle) and maps colored according to local resolution (right) for the GABAB receptor in the presence of CGP54626 (slate; antagonist) (a) and in complex with baclofen (magenta; agonist), BHFF (steel blue; PAM) and Gi1 protein (b). The colored density map is a composite map generated with the VFT and TMD locally refined map. The cryo-EM density map before focused refinement in transparent superposed with the final map, illustrating density for detergent micelle and Gi1 protein. The local resolution (Å) was calculated with the locally refined map as input, indicating a range of 2.5–3.5 Å resolution in most map regions for both the inactive and active states. GB1 and GB2 in inactive state, blue and yellow, respectively; red and green in active state, respectively.

Article Snippet: The high-resolution cryo-EM maps not only confirmed the binding mode of {"type":"entrez-protein","attrs":{"text":"CGP54626","term_id":"875260408","term_text":"CGP54626"}} CGP54626 and baclofen observed in the crystal structures of GABA B VFT, 29 but also revealed the working mechanism of BHFF as PAM agonist, which stabilizes a novel intersubunit interface in the TM domains of the active GABA B receptor.

Techniques: Cryo-EM Sample Prep, Generated

Journal: Aging (Albany NY)

Article Title: Ginsenoside Rb1 regulates prefrontal cortical GABAergic transmission in MPTP-treated mice

doi: 10.18632/aging.102095

Figure Lengend Snippet: Rb1 modulates GABA B receptor in the PFC of MPTP-treated mice. ( A ) Overall map of Rb1 interaction with GABA B R1 receptor. ( B ) Interaction between Rb1 with the extracellular domain of 4MS1, agonist conformation of GABA B R1 receptor. Note that when Rb1 (indicted by green stick) was docked in the extracellular domain of 4MS1, four hydrogen bonds formed with the amino group of main chain and hydroxyl group of side chain of Ser130 sites, the amino group of main chain of Ser131 site, and the side chain of Asp104 site (indicated by red dotted line). Besides, Rb1 also formed a hydrophobic interaction with multiple hydrophobic amino acids or hydrophobic parts of polar amino acids in the extracellular domain of 4MS1 (Cys103, Cys129, Trp65, His170, Ser153, Tyr250, Val201) (indicated by blue stick). ( C and D ) The effect of Rb1 on the GABA B receptor expression in the synaptosome and PSD fraction of the PFC of MPTP-treated mice was determined by western blotting. Western blotting results are from two of the six mice in each group and are expressed as the mean ± SEM of three experiments. ( E ) Representative traces of GABA receptor-mediated mIPSCs in the presence of Rb1 and GABA B -receptor agonist Baclofen. All mIPSCs were recorded at a holding potential of −65 mV. ( F ) Cumulative frequency plots of the inter-event interval (left) and quantitative analysis of the frequency of GABA receptor-mediated mIPSCs (right) in the presence of Rb1 and presence of Baclofen. ( G ) Cumulative frequency plots (left) and quantitative analysis (right) of the amplitude of GABA receptor-mediated mIPSCs in the presence of Rb1 and presence of Baclofen. n = 14–20 per group. ** P < 0.01 and * P < 0.05 vs. control; ## P < 0.01 and # P < 0.05 vs. MPTP group; & P < 0.05 vs. MPTP+Rb1 group. Statistical significance was determined by one-way ANOVA and the Bonferroni post-hoc test for pairwise comparisons.

Article Snippet: Antibodies for anti-vGAT, anti-integrin, as well as the GABA B -receptor agonist Baclofen, were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA).

Techniques: Expressing, Western Blot, Control

Journal: Molecular Medicine Reports

Article Title: The GABAB receptor agonist STX209 reverses the autism-like behaviour in an animal model of autism induced by prenatal exposure to valproic acid

doi: 10.3892/mmr.2022.12670

Figure Lengend Snippet: Treatment with STX209 ameliorates sociability deficits and preference for social novelty deficits in VPA model mice. (A) Representative trace and heatmap images from tested mice in scene 1 in the social interaction test (E, empty; S1, stranger 1). (B) Time that tested mice entered the region containing stranger 1 for sniffing in scene 1. (C) Time that tested mice entered the empty cage region for sniffing in scene 1. (D) Representative trace and heatmap images from tested mice in scene 2 in the social interaction test (E, empty; S1, stranger 1; S2, stranger 2). (E) Time that tested mice entered the region containing stranger 2 for sniffing in scene 2. (F) Time that tested mice entered the region containing stranger 1 for sniffing in scene 2. (G) Total time that tested mice entered the region containing stranger 2 and stranger 1 for sniffing in scene 2. (H) SPI of tested mice in scene 2. *P<0.05, **P<0.01, ***P<0.001 (two-way ANOVA followed by Bonferroni post hoc test). All data are presented as the mean ± SEM. Each group had 14 mice. CTRL, control; NS, normal saline; SPI, social preference index; VPA, valproic acid; ns, no significance.

Article Snippet: STX209 (MedChemExpress) was administered intraperitoneally to CTRL+STX20 and VPA+STX209 group mice at a dose of 0.6 mg/kg in 0.9% NS twice a day from weaning (P21) until the end of the experiment (approximately P60) ( ).

Techniques: Control, Saline

Journal: Molecular Medicine Reports

Article Title: The GABAB receptor agonist STX209 reverses the autism-like behaviour in an animal model of autism induced by prenatal exposure to valproic acid

doi: 10.3892/mmr.2022.12670

Figure Lengend Snippet: STX209 ameliorates the novelty recognition deficits of VPA model mice. (A) Representative trace and heatmap images from tested mice in scene 1 in the novel object recognition task. (B) Representative trace and heatmap images from tested mice in scene 2 in the novel object recognition task. This test was used to assess novelty recognition ability. (C) Total time spent sniffing the two similar objects by each group of mice in scene 1. (D) Time spent sniffing the novel object by each group of mice in scene 2. (E) DI of each group of mice in scene 2. *P<0.05, **P<0.01, ***P<0.001 (two-way ANOVA followed by Bonferroni post hoc test). All data are presented as the mean ± SEM. Each group had 14 mice. CTRL, control; DI, discrimination index; NS, normal saline; VPA, valproic acid; ns, no significance.

Article Snippet: STX209 (MedChemExpress) was administered intraperitoneally to CTRL+STX20 and VPA+STX209 group mice at a dose of 0.6 mg/kg in 0.9% NS twice a day from weaning (P21) until the end of the experiment (approximately P60) ( ).

Techniques: Control, Saline

Journal: Molecular Medicine Reports

Article Title: The GABAB receptor agonist STX209 reverses the autism-like behaviour in an animal model of autism induced by prenatal exposure to valproic acid

doi: 10.3892/mmr.2022.12670

Figure Lengend Snippet: STX209 ameliorates the locomotion and exploratory activity deficits of VPA model mice. (A) Representative trace and heatmap images from tested mice in the open-field task (task 1). (B) Representative trace and heatmap images from tested mice in the open-field habituation task (task 2). (C) Time travelled in the inner zone by mice in the two open-field tasks. (D) Distance travelled by mice in the inner zone in the two open-field tasks. (E) OFEI of mice in the two open-field tasks. ***P<0.001 (Student's paired t-test was used to compare the differences in behaviour in every group of mice between the two tasks, and three-way mixed ANOVA followed by Bonferroni post hoc test was used to compare the difference in same task among four group). All data are presented as the mean ± SEM. Each group had 14 mice. CTRL, control; OFEI, open-field exploration index; NS, normal saline; VPA, valproic acid; ns, no significance.

Article Snippet: STX209 (MedChemExpress) was administered intraperitoneally to CTRL+STX20 and VPA+STX209 group mice at a dose of 0.6 mg/kg in 0.9% NS twice a day from weaning (P21) until the end of the experiment (approximately P60) ( ).

Techniques: Activity Assay, Control, Saline

Journal: Molecular Medicine Reports

Article Title: The GABAB receptor agonist STX209 reverses the autism-like behaviour in an animal model of autism induced by prenatal exposure to valproic acid

doi: 10.3892/mmr.2022.12670

Figure Lengend Snippet: STX209 ameliorates marble burying deficits in VPA model mice. (A) Representative marble burying maps. (B) Numbers of buried marbles of each group of mice in the 10-min test. (C) Number of burying actions (strong and obvious digging or burial movement) for each group of mice in the 10-min test. ***P<0.001 (two-way ANOVA followed by Bonferroni post hoc test). All data are presented as the mean ± SEM. Each group had 14 mice. (D) Correlation analysis between the number of buried marbles and the number of burying actions was conducted using Pearson correlation analysis and linear regression analysis. All mice (n=56) were included in the analysis, and there was a linear correlation between the number of buried marbles and the number of burying actions. CTRL, control; VPA, valproic acid.

Article Snippet: STX209 (MedChemExpress) was administered intraperitoneally to CTRL+STX20 and VPA+STX209 group mice at a dose of 0.6 mg/kg in 0.9% NS twice a day from weaning (P21) until the end of the experiment (approximately P60) ( ).

Techniques: Control

Journal: Molecular Medicine Reports

Article Title: The GABAB receptor agonist STX209 reverses the autism-like behaviour in an animal model of autism induced by prenatal exposure to valproic acid

doi: 10.3892/mmr.2022.12670

Figure Lengend Snippet: Prenatal VPA exposure impairs neuronal development in the DG/CA1 in the hippocampi of offspring mice and STX209 ameliorates these neuronal structural defects. Representative reconstructions of the dendrites of (A) DG and (D) CA1 neurons in the hippocampus in the four groups (scale bar, 50 µm), concentric circles are 5 µm apart. Representative maps of dendritic spines at the ends of basal dendrites (tertiary dendrites) of (C) DG and (F) CA1 neurons in the four groups of mice. Arrows indicate the mushroom spine (scale bar, 5 µm). Total length of dendrites of (B) DG and (E) CA1 neurons in the four groups. Density of (G and I) total spines and (H and J) mushroom spines at the end of the basal dendrites (tertiary dendrites) of pyramidal neurons in the DG and CA1 regions of the hippocampus of the four groups (n=27/group). ***P<0.001 (two-way ANOVA followed by Bonferroni post hoc test). All data are presented as the mean ± SEM. CTRL, control; DG, dentate gyrus; VPA, valproic acid; ns, no significance.

Article Snippet: STX209 (MedChemExpress) was administered intraperitoneally to CTRL+STX20 and VPA+STX209 group mice at a dose of 0.6 mg/kg in 0.9% NS twice a day from weaning (P21) until the end of the experiment (approximately P60) ( ).

Techniques: Control

Journal: Molecular Medicine Reports

Article Title: The GABAB receptor agonist STX209 reverses the autism-like behaviour in an animal model of autism induced by prenatal exposure to valproic acid

doi: 10.3892/mmr.2022.12670

Figure Lengend Snippet: Prenatal VPA exposure causes GABAergic system function defects in the hippocampus of VPA model mice, and nervous system damage in the CA1 and DG regions of the hippocampus in the mice. STX209 ameliorates these defects. Representative western blotting images showing the expression levels of (A) GABABR2 and (B) GAD65/67 protein in the entire hippocampus in each group. Histograms of the relative expression levels of (C) GABABR2 and (D) GAD65/67 proteins in each group (n=3 mice from different mothers/group; western blotting was repeated once). Chronic administration of STX209 did not increase GAD65/67 expression in VPA model mice but elevated the expression level of GABABR2. **P<0.01, ***P<0.001 (two-way ANOVA followed by Bonferroni post hoc test). All data are presented as the mean ± SEM. CTRL, control; NS, normal saline; GABABR2, γ-aminobutyric acid type B receptor 2; GAD65/67, glutamic acid decarboxylase 65/67; VPA, valproic acid; ns, no significance.

Article Snippet: STX209 (MedChemExpress) was administered intraperitoneally to CTRL+STX20 and VPA+STX209 group mice at a dose of 0.6 mg/kg in 0.9% NS twice a day from weaning (P21) until the end of the experiment (approximately P60) ( ).

Techniques: Western Blot, Expressing, Control, Saline