vu0810464  (MedChemExpress)

Journal: bioRxiv

Article Title: Low dose of a non-urea selective GIRK channel activator improves hippocampal-dependent synaptic plasticity and memory disrupted by amyloid-β oligomers

doi: 10.1101/2024.11.05.622060

Figure Lengend Snippet: (A) A guide cannula was implanted for icv. drug administration on the left ventricle, which was later histologically verified (asterisk, *, indicates cannula’s location). Scale bar: 500 μm. ( B) On day 0, after surgery recovery, a single icv. injection of oA β 1–42 was administered to set up a non-transgenic model of early AD-like amyloidosis in the dorsal hippocampus. Control sham animals were icv . injected with PBS. (C-D) Selective GIRK channel activator VU0810464 (VU) or its vehicle were administered daily 30 min before behavioral testing. (C) On day 1 post-oA β or sham PBS icv. delivery, animals received an icv . injection of low or high dose of VU or its vehicle before the training session for the Object Location memory (OLM) task. Five hours after training, a short-term memory test session (OLM 1) was performed. On day 2 post amyloidosis induction by oA β , animals received another icv . injection of low or high dose of VU before a test session for long-term memory retrieval (OLM 2) was conducted. (D) On day 3 post-oA β injection, animals received the corresponding VU treatment and anxiety levels were measured using the Elevated Plus Maze. (E) Ex vivo hippocampal LTP was studied using multi-electrode arrays (MEAs) electrophysiology in hippocampal horizontal slices (days 4–17 post-oA β injection) adding VU at low or high doses to the perfusion system. Representative location of stimulation (St., orange) and recording (Rec., yellow) electrodes in a hippocampal horizontal slice. icv ., intracerebroventricular; LV, lateral ventricle; D, dorsal, M, medial.

Article Snippet: To pharmacologically modulate GIRK channels activity, we employed VU0810464 (#HY-127106; MedChemExpress, US), a selective non-urea-based activator of GIRK1/2 channels ( ).

Techniques: Injection, Transgenic Assay, Control, Ex Vivo

Journal: bioRxiv

Article Title: Low dose of a non-urea selective GIRK channel activator improves hippocampal-dependent synaptic plasticity and memory disrupted by amyloid-β oligomers

doi: 10.1101/2024.11.05.622060

Figure Lengend Snippet: (A) Multi-electrode arrays (MEAs) electrophysiology was performed to study the effect of low or high concentration of VU0810464 (VU) on hippocampal LTP after oA β 1–42 injection. VU or its vehicle were perfused in the recording chamber. (B) Representative averaged (n = 5-6) traces of fEPSPs recorded in the CA1 area, collected during the baseline (1) and ≈60 min post-HFS (2). (C, D) Time course of the LTP evoked in the CA1 area after a HFS protocol in hippocampal slices from (C) sham + vehicle, sham + VU 10µM and sham + VU 5µM and from (D) oA β + vehicle, oA β + VU 10µM or oA β + VU 5µM treated mice. (E, F) Bars illustrate mean ± SEM fEPSPs amplitude of the last 10 min of the recording from the same groups illustrated in C and D, respectively. * p < 0.05, ** p < 0.01, *** p < 0.001 vs . sham + VU 10µM (D) or vs . oA β + vehicle (F). St., stimulation electrode; Rec., recording electrode.

Article Snippet: To pharmacologically modulate GIRK channels activity, we employed VU0810464 (#HY-127106; MedChemExpress, US), a selective non-urea-based activator of GIRK1/2 channels ( ).

Techniques: Concentration Assay, Injection

Journal: bioRxiv

Article Title: Low dose of a non-urea selective GIRK channel activator improves hippocampal-dependent synaptic plasticity and memory disrupted by amyloid-β oligomers

doi: 10.1101/2024.11.05.622060

Figure Lengend Snippet: (A) An OLM test was performed, changing the location of one object between the training and each memory test (OLM 1 and OLM 2). oA β 1–42 or sham (PBS) were administered icv. the day before training (day 0), and either vehicle or low or high doses of VU0810464 (VU) were icv .-injected daily 30 min before the behavioral task (days 1 and 2). (B-C) Discrimination index during training, OLM 1, and OLM 2 sessions for (B) sham + vehicle, sham + VU 0.75mM and sham + VU 1.5mM mice and (C) oA β + vehicle, oA β + VU 0.75mM and oA β + VU 1.5mM groups. Data are expressed as the mean ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001 vs . sham + VU 1.5mM (B) or vs. oA β + vehicle (C); # p < 0.05, ## p < 0.01, ### p < 0.001 comparing oA β + vehicle vs. sham + vehicle.

Article Snippet: To pharmacologically modulate GIRK channels activity, we employed VU0810464 (#HY-127106; MedChemExpress, US), a selective non-urea-based activator of GIRK1/2 channels ( ).

Techniques: Injection

Journal: bioRxiv

Article Title: Low dose of a non-urea selective GIRK channel activator improves hippocampal-dependent synaptic plasticity and memory disrupted by amyloid-β oligomers

doi: 10.1101/2024.11.05.622060

Figure Lengend Snippet: (A) The EPM was used to evaluate the effect of VU0810464 (VU) treatment on the general health state of the animals, on day 3 post-oA β 1–42 or sham (PBS) injection. (B) Percentage (%) of entries in open arms were measured to evaluate anxiety levels. (C) Total distance traveled was used as a measure of locomotor activity for (left) sham + vehicle, sham + VU 0.75mM and sham + VU 1.5mM treated mice and for (right) oA β + vehicle, oA β + VU 0.75mM and oA β + VU 1.5mM groups.

Article Snippet: To pharmacologically modulate GIRK channels activity, we employed VU0810464 (#HY-127106; MedChemExpress, US), a selective non-urea-based activator of GIRK1/2 channels ( ).

Techniques: Injection, Activity Assay