PEPDIA-PLP-002974

Fig. 2A: TpNPY at concentrations of 6–25 μM did not lead to any substantial changes in the survival rate of zebrafish larvae. However, once the concentration arrived at 40 μM, the mortality rate of zebrafish larvae sharply increased, reaching approximately 50%.

Fig. 2B: the application of 10 mM PTZ dramatically altered the swimming pattern of the zebrafish, as reflected by the increased distance traveled at high speed, whereas these abnormal seizure-like behavior phenotypes were abolished under the treatment of TpNPY (0.75–6 μM).

Fig. 2D and E: the mRNA expression levels of these two genes were significantly upregulated in response to PTZ treatment. However, treatment with TpNPY successfully reversed this overexpression.

Fig. 3A: after 15 injections, the seizure score in PTZ-treated group arrived at 4.91±0.41; whereas TpNPY treatment at 0.25, 0.5, and 1 mg/kg reduced the seizure score to 4.69±0.32, 3.60±0.47, and 2.62±0.35, respectively.

Fig. 3B and C: TpNPY dose-dependently augmented the latency to seizure generation, as well as decreased the duration of generalized seizures.

Fig. 4A-C: PTZ-treated mice displayed significantly increased anxiety-like behaviors... TpNPY administration substantially reversed these behavioral deficits.

Fig. 4D and E: PTZ-treated mice exhibited a significantly lower discrimination index... TpNPY treatment restored this cognitive deficit.

Fig. 4F-K: PTZ-treated mice showed prolonged escape latencies and fewer platform crossings... TpNPY treatment ameliorated these spatial memory impairments.

Fig. 5A: chronic exposure to PTZ suppressed the neurogenesis in the hippocampal dentate gyrus (DG) in mice... whereas the application of TpNPY significantly promotes the neurogenesis.

Fig. 5B-D: PTZ treatment significantly decreased the expression levels of TrkB and BDNF, while the administration of TpNPY dose-dependently upregulates these two proteins.

Fig. 5E: TpNPY promotes neural synaptic plasticity as depicted in Fig. 5E.

Fig. 6C-E: the reduced cell viability triggered by glutamate was restored by the incubation of TpNPY, as verified by the MTT assay, LDH assay and live-dead cell staining assay.

Fig. 6F-H: glutamate stimulation significantly decreased the expression of Bcl-2 and increased the expression of Bax in HT22 cells, while treatment with TpNPY abolished these effects.

Fig. 7E-H: the application of TpNPY dramatically prevented glutamate-induced calcium overload and ROS accumulation.

Fig. 7I-K: TpNPY dose-dependently upregulated the protein levels of Nrf2 and HO-1... a significant enhancement in the nuclear translocation of Nrf2 in HT22 cells following the application of TpNPY.

Fig. 1F: the surface plasmon resonance (SPR) analysis revealed a direct interaction between TpNPY and NPY-Y1R, with an equilibrium dissociation constant of 1.98 μM.

Fig. 2C and F: the ROS levels in zebrafish larvae upregulated dramatically following PTZ challenge. Nevertheless, treatment with TpNPY mitigated the overaccumulation of ROS elicited by PTZ effectively.

Fig. 7A-D: SOD activity, MDA and GSH concentration in the glutamate-treated group reduced sharply and GSH concentration increased dramatically, whereas these effects were effectively counteracted by the application of increasing concentration of TpNPY.

Fig. 3D-F: PTZ administration significantly upregulated the expression levels of IL-6, IL-1β, and TNF-α in the mouse hippocampus... In contrast, TpNPY treatment effectively reversed these PTZ-induced elevations in proinflammatory cytokine expression.

Fig. 3G-I: the protein expression of GFAP and Iba-1 in the ventral hippocampus of mice was significantly increased upon subconvulsive dose of PTZ... however, these upregulation trends were counteracted by the application of TpNPY.

Fig. 6A: TpNPY ranging from 1.56 to 50 μM did not elicit any significant changes in cell viability after 24 h incubation.