In cultured rat hippocampal neurons, 1 μM BMS-299897 for 24 h impaired retrograde transport of quantum-dot-labeled BDNF relative to vehicle. The reported mean instantaneous retrograde velocity fell from approximately 0.8 to 0.3 μm/s, and transport distance decreased by about 40%. These findings identify a neuronal functional liability under the tested conditions. [1]
APP and N-cadherin processing in rat cortical neurons
Cell-based study · Primary embryonic rat E18 cortical neurons; Aβ concentration-response at DIV7 [1]
After 24 h, BMS-299897 reduced released Aβ38, Aβ40 and Aβ42 and increased APP and N-cadherin C-terminal fragments relative to vehicle.
Literature-Reported Treatment Conditions
- Treatment concentration
- BMS-299897 concentration-response; ∼1.0 μM for reported Aβ range; 1 μM for Fig. 1E
- Exposure duration
- 24 h
- Method
- Added to neuronal culture medium
- Vehicle
- 0.1% DMSO final; vehicle control
- Co-treatment
- No combination treatment; sGSM41 2.5 μM was a separate comparator for Fig. 1E
- Reported limits
- No compound lot, analytical purity or independent stereochemical confirmation reported in the acquired Reagents section.
Methods and source locations
Compound reported in the paper: BMS-299897; Compound label in the paper: BMS-299897
Effects of the reported research compound in cultured rat neurons; no Adooq lot validation.
Fig. 1C and 1E and caption; first Results subsection; Methods: Antibodies and Reagents, Drug treatments, Aβ Meso scale assay, immunoblotting
Aβ38, Aβ40 and Aβ42 in conditioned medium relative to vehicle: Aβ triplex Meso Scale assay; 24-h conditioned medium; n = 3 in Fig. 1 caption; range reported in Results, not estimated from curves — Fig. 1C and caption; first Results subsection; Aβ Meso scale assay
APP and N-cadherin C-terminal fragments: Immunoblotting against vehicle and sGSM41 comparator; β-tubulin loading control in Fig. 1E — Fig. 1E and caption; first Results subsection
Impaired BDNF axonal transport in cultured rat hippocampal neurons
Cell-based study · Rat E18 hippocampal neurons in compartmentalized microfluidic chambers; drug treatment at DIV7 [1]
BMS-299897 slowed retrograde QD-BDNF transport, reduced distance travelled, and shifted directional movement toward anterograde trajectories. The separate sGSM41 comparator did not significantly alter the corresponding transport measures.
Literature-Reported Treatment Conditions
- Treatment concentration
- 1 μM BMS-299897
- Exposure duration
- 24 h drug pretreatment
- Method
- Culture treatment followed by live QD-BDNF transport imaging; distal QD-BDNF 0.1 nM, 2 h incubation in Live Imaging methods
- Vehicle
- 0.1% DMSO final
- Co-treatment
- QD-BDNF was the transport probe; sGSM41 2.5 μM was a separate comparator
- Reported limits
- Methods state at least two experiments and 75–130 signals; Fig. 2 caption specifies at least three experiments and 70–125 molecules for plotted velocity data. Movies were not viewed; imaging-duration descriptions vary (2 min Methods, 90 s illustrated kymograph). These are not animal sample sizes.
Methods and source locations
Compound reported in the paper: BMS-299897; Compound label in the paper: BMS-299897
Effects of the reported research compound in cultured rat neurons; no Adooq lot validation.
Fig. 2B–E and caption; Results: BMS-299897, but not sGSM41, induced deficits in retrograde axonal transport; Methods: neuronal cultures, Drug treatments, Live Imaging of QD-BDNF, Statistical analysis
Instantaneous retrograde velocity of moving QD-BDNF: Blinded live imaging and kymographs; approximate means explicitly stated in Results; Fig. 2C represents 70–125 QD-BDNF molecules from at least three independent experiments per caption — Fig. 2B–C and caption; BDNF transport Results
Average distance travelled by QD-BDNF: Kymograph analysis; mean ± S.E. from three independent experiments; Student’s t-test per Fig. 2D–E caption — Fig. 2D and caption; BDNF transport Results
Distribution of QD-BDNF movement directions: Directionality classified from kymographs; mean ± S.E. from three independent experiments; sGSM41 had no significant directional effect — Fig. 2E and caption; BDNF transport Results
