nmdar antagonist memantine  (MedChemExpress)

Journal: International Journal of Molecular Sciences

Article Title: Neuronal TCF7L2 in Lateral Habenula Is Involved in Stress-Induced Depression

doi: 10.3390/ijms252212404

Figure Lengend Snippet: NMDAR was involved in TCF7L2-mediated depressive-like behavior. ( A ) Experimental timeline for NMDAR agonist-NMDA administration and behavioral tests. ( B ) Effects of NMDA administration on latency to the first immobility in the TST with LHb neurons special TCF7L2 knockdown, mean of AAV-sh-scrambled + Saline: 106, mean of AAV-sh-scrambled + NMDA: 111.9, mean of AAV-sh-TCF7L2 + Saline: 111.1, mean of AAV-sh-TCF7L2 + NMDA: 108.8. ( C ) Total immobility time in the TST, mean of AAV-sh-scrambled + Saline: 57.75, mean of AAV-sh-scrambled + NMDA: 52.45, mean of AAV-sh-TCF7L2 + Saline: 8.143, mean of AAV-sh-TCF7L2 + NMDA: 62.63. ( D ) Effects of NMDA administration on latency to the first floating in the FST, mean of AAV-sh-scrambled + Saline: 72.36, mean of AAV-sh-scrambled + NMDA: 95.45, mean of AAV-sh-TCF7L2 + Saline: 110.9, mean of AAV-sh-TCF7L2 + NMDA: 102.6. ( E ) Total floating time in the FST, mean of AAV-sh-scrambled + Saline: 106.1, mean of AAV-sh-scrambled + NMDA: 120.7, mean of AAV-sh-TCF7L2 + Saline: 45, mean of AAV-sh-TCF7L2 + NMDA: 134.7. ( F ) Experimental timeline for NMDAR antagonist-memantine administration and behavioral tests. ( G ) Effects of memantine administration on latency to the first immobility in the TST with LHb neurons special TCF7L2 overexpression, mean of AAV-EGFP + Saline: 85.25, mean of AAV-EGFP + Memantine: 88.25, mean of AAV-TCF7L2 + Saline: 50.75, mean of AAV-TCF7L2 + Memantine: 80.05. ( H ) Total immobility time in the TST, mean of AAV-EGFP + Saline: 79.75, mean of AAV-EGFP + Memantine: 75.38, mean of AAV-TCF7L2 + Saline: 131.5, mean of AAV-TCF7L2 + Memantine: 72.38. ( I ) Effects of memantine administration on latency to the first floating in the FST, mean of AAV-EGFP + Saline: 91.5, mean of AAV-EGFP + Memantine: 100.8, mean of AAV-TCF7L2 + Saline: 35, mean of AAV-TCF7L2 + Memantine: 82.5. ( J ) Total floating time in the FST, mean of AAV-EGFP + Saline: 32.25, mean of AAV-EGFP + Memantine: 44.63, mean of AAV-TCF7L2 + Saline: 157.5, mean of AAV-TCF7L2 + Memantine: 77.88. Comparisons between groups were conducted using one-way ANOVA. Data are expressed as means ± SEM. n = 7–11 per group. * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: The mice in these groups received intraperitoneal injections of the NMDAR agonist NMDA (75 mg/kg, MCE, HY-17551), or the NMDAR antagonist memantine (15 mg/kg, MCE, HY-B0365A), or saline as a solvent.

Techniques: Knockdown, Saline, Over Expression

Journal: Communications Biology

Article Title: Synaptic potentiation of engram cells is necessary and sufficient for context fear memory

doi: 10.1038/s42003-025-08140-6

Figure Lengend Snippet: A The cfos-shEGFP transgenic mouse, expressing a short half-life (sh)EGFP under the control of the cfos promoter. B Experimental design in which the cfos-shEGFP mouse was either used for whole-cell recordings or memory recall tests after different behavior treatments. Ctxt context, EC external capsule, IC internal capsule, BLA basolateral amygdala. C Freezing response to the context (blue bars) and/or tone (orange bars) measured 24 h after correspondent behavior treatment. N = 8 per group, except in “Context only” group, in which N = 6. D Whole-cell recording design. Panel I shows stimulating electrode over internal capsule fiber bundle. II and III illustrate ongoing whole-cell recording (red asterisk) of a GFP + neuron. IV-VI are confocal images of neighboring neurons filled with Alexa 594 during recordings: the GFP + neuron is highlighted by a yellow arrow, while the GFP − is highlighted by a cyan arrow. Scale bars: 50 µm. These images were taken from a slice of an Arc-tTA/TetO-H2B-GFP mouse ( F ). E AMPAR/NMDAR ratio of GFP + vs GFP − BLA neurons from acute brain slices of cfos-shEGFP mice sac’ed 90 min after behavior treatment. An increase in AMPAR/NMDAR ratio was only observed after successful conditioning and was restricted to GFP + neurons. N = 6–9 per group. F Arc-tTA x TetO-H2BGFP double transgenic mouse, in which the tetracycline transactivator (tTA) was knocked in the Arc gene and controls the expression of the long-lasting histone-bound GFP. G Experimental design illustrating the tagging window of the Arc-tTA/TetO-H2B-GFP mouse line, controlled by the presence of Doxycycline (Dox) in the food. Tagged neurons were recorded 7 days after. Correspondent behavior result can be found on Supplementary Fig. . H Specific AMPAR/NMDAR ratio increase in GFP + neurons following conditioning is maintained for at least 7 days. CFC Contextual fear conditioning. N = 8, 9 per group. ** P < 0.01, **** P < 0.0001, one-way ANOVA with Tukey test ( C ), unpaired t test [( E ) and ( H )]. Graph bars show mean +/−SEM.

Article Snippet: Once a stable baseline of EPSCs (compound AMPAR + NMDAR current) was established, an NMDAR antagonist AP5 (50 μM, Tocris) was applied for 5 min and AMPAR EPSCs were recorded in the presence of AP5.

Techniques: Transgenic Assay, Expressing, Control

Journal: Communications Biology

Article Title: Synaptic potentiation of engram cells is necessary and sufficient for context fear memory

doi: 10.1038/s42003-025-08140-6

Figure Lengend Snippet: A rAAV-DJ carrying a DIO-(wild-type or mutant) CaMKIIα-2A-H2BGFP construct was injected bilaterally in the BLA of cfos-DD-Cre (FDC) mice, in which Cre-recombinase is fused to a destabilizing domain (DD), which leads to protein degradation. The drug trimethoprim lactate (TMP) stabilizes the complex, allowing Cre to activate the CaMKIIα construct along with the H2B-GFP marker in cfos + BLA neurons. B , C Representative coronal BLA sections showing H2B-GFP induction 14 days after TMP or vehicle (saline) IP injection, quantified in ( C ). N = 6 mice per group. Scale bar: 200 μm. D Experimental design to test whether CK2-D impairs memory recall. E CK2-D expression in cfos + BLA neurons tagged during context conditioning reverses learning-induced AMPAR/NMDAR ratio increase. No tone conditioning/exposure was performed in order to allow for clearer interpretation of the effect of CK2-D expression on context conditioning-induced plasticity. N = 7, 8 neurons per group. F , G CK2-D expression in cfos + BLA neurons tagged during training impairs long-term memory, as opposed to WT-CK2. N = 6 mice per group. H , I Representative coronal BLA sections showing overlap between activity markers during training (H2B-GFP) and context recall [(cfos IHC), ( H )], quantified in ( I ). CK2-D reversal of synaptic potentiation impaired reactivation of learning-induced neurons. OL: overlap. N = 6 mice per group. Scale bar: 20 μm. J Experimental design to test context specificity. K CK2-D-mediated memory impairment is specific to tagged context. N = 6, 7 per group. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns not significant; one-way ANOVA with Tukey test [( C ), ( I ) and ( K )], unpaired t-test ( E ), or two-way RM ANOVA with Tukey test [( F ) and ( G )]. Graphs show mean +/−SEM.

Article Snippet: Once a stable baseline of EPSCs (compound AMPAR + NMDAR current) was established, an NMDAR antagonist AP5 (50 μM, Tocris) was applied for 5 min and AMPAR EPSCs were recorded in the presence of AP5.

Techniques: Mutagenesis, Construct, Injection, Marker, Saline, Expressing, Activity Assay

Journal: Communications Biology

Article Title: Synaptic potentiation of engram cells is necessary and sufficient for context fear memory

doi: 10.1038/s42003-025-08140-6

Figure Lengend Snippet: A rAAV-DJ carrying a DIO-CK2-2A-H2BGFP construct was injected bilaterally in the BLA of FDC mice. B Experimental design to test whether CK2-DAA induces synaptic potentiation in the BLA in the absence of US exposure. C CK2-DAA expression induces increase in AMPAR/NMDAR ratio, whereas WT-CK2 overexpression does not affect it. D Experimental design to test whether CK2-DAA mediated-potentiation creates a de novo memory association. E Experimental groups and their respective tagging regimes, with either TMP or Veh IP injected 20 min after each behavior exposure. Mice in the ON hab group were kept overnight in box A before shock exposure to prevent any conditioning (Fig. ). N = 8 mice per group, except in the Veh group, where N = 7. F – H CK2-DAA potentiation of US neurons led to indiscriminate fear associations, including the untagged box C ( F ). I , J Representative coronal BLA sections showing overlap between activity markers during exposure (H2B-GFP) and recall to the untagged box C [(cfos IHC), ( I )], quantified in ( J ). OL overlap. Scale bar: 20 mm. ** P < 0.01, *** P < 0.001, **** P < 0.0001, ns not significant; unpaired t-test ( C ), two-way RM ANOVA with Tukey test [( F )–( H )] or one-way ANOVA with Tukey test ( J ). Graphs show mean +/− SEM.

Article Snippet: Once a stable baseline of EPSCs (compound AMPAR + NMDAR current) was established, an NMDAR antagonist AP5 (50 μM, Tocris) was applied for 5 min and AMPAR EPSCs were recorded in the presence of AP5.

Techniques: Construct, Injection, Expressing, Over Expression, Activity Assay

Journal: Redox Biology

Article Title: Nobiletin regulates intracellular Ca 2+ levels via IP 3 R and ameliorates neuroinflammation in Aβ42-induced astrocytes

doi: 10.1016/j.redox.2024.103197

Figure Lengend Snippet: Nobiletin regulates intracellular Ca 2+ levels by regulating P2Y1, P2Y2, α7nAChR, mGLUR5, and NMDAR in Aβ42-induced primary astrocytes. (A–D) Primary rat astrocytes were exposed to 4 μM Aβ42 alone and in combination with purinergic antagonist (PPADS, 100 μM), NMDAR antagonist (D-AP5, 50 μM), mGLUR antagonist (MPEP, 50 μM), and α7nAChR antagonist (MLA, 5 μM) for 50 min. (E–F) Primary astrocytes were treated with 4 μM Aβ42 in the absence and presence of 40 μM NOB alone or in combination with NMDAR agonist (TZG, 10 μM), purinergic agonist (ATP disodium salt, 10 μM), mGluR5 agonist (CHPG sodium salt, 10 μM), and αnAChR agonist (PNU 282987, 10 μM) for 50 min, and intracellular calcium levels were observed using the Fura-2A assay. Con, control; Aβ42, amyloid beta-42; NOB, nobiletin; PPADS, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid; MPEP, 2-methyl-6-(phenylethynyl)-pyridine hydrochloride; MLA, methyllycaconitine citrate; TZG, D,L-(tetrazol-5-yl)glycine. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Article Snippet: Primary antibodies for TLR4 (ab22048), P2Y2 (ab272891), NMDAR1 (ab109182), NMDAR2 (ab133265), and IP 3 R (ab108517), and the Fura-2 calcium flux assay kit (ab176766), DCFDA/H2DCFDA cellular ROS assay kit (ab113851), Aβ42 peptide (ab120301), P2 purinergic receptor antagonist (PPADS, ab120009), mGLUR5 antagonist (MPEP hydrochloride, ab120008), NMDAR antagonist (D-AP5, ab120003), and α7nAChR antagonist (methyllycaconitine citrate (MLA), ab120072) were purchased from Abcam (Cambridge, UK).

Techniques: