Protective Roles of N-trans-feruloyltyramine Against Scopolamine-Induced Cholinergic Dysfunction on Cortex and Hippocampus of Rat Brains

Objective: To study the protective effects of N-trans-feruloyltyramine (NTF) on scopolamine-induced cholinergic dysfunction, apoptosis, and inflammation in rat brains. Materials and Methods: Treatments were administered intraperitoneally (i.p.). Wistar rats (8-week-old) were allocated into 4 groups (n = 3) as follows: scopolamine-only, NTF-only, NTF + scopolamine and control. Spatial cognition was evaluated by Morris water maze. ROS assay and Western blot analyses were conducted in 3 brain regions: the frontal cortex, hippocampus, and temporal cortex. Results: NTF treatment inhibited scopolamine-induced memory impairment and significantly attenuated scopolamine-induced changes in the three brain regions. Investigated scopolamine-associated changes were as follows: increases in ROS production and BACE1 level, decrease in ChAT level, increases in inflammatory and apoptotic markers, and activation of signaling pathway kinases related to inflammation and apoptosis. Conclusion: With its in vivo antioxidant, cholinergic-promoting, anti-apoptosis, and anti-inflammatory biological activities, NTF is a promising candidate to be further investigated as a potential treatment for Alzheimer’s-associated neurodegeneration

Brain-derived neurotrophic factor increases cell number of neural progenitor cells derived from human induced pluripotent stem cells

Background Several pieces of evidence from in vitro studies showed that brain-derived neurotrophic factor (BDNF) promotes proliferation and differentiation of neural stem/progenitor cells (NSCs) into neurons. Moreover, the JAK2 pathway was proposed to be associated with mouse NSC proliferation. BDNF could activate the STAT-3 pathway and induce proliferation in mouse NSCs. However, its effects on proliferation are not fully understood and JAK/STAT pathway was proposed to play a role in this activity. Methods In the present study, the effects of BDNF on cell proliferation and neurite outgrowth of Alzheimer’s disease (AD) induced pluripotent stem cells (iPSCs)-derived human neural progenitor cells (hNPCs) were examined. Moreover, a specific signal transduction pathway important in cell proliferation was investigated using a JAK2 inhibitor (AG490) to clarify the role of that pathway. Results The proliferative effect of BDNF was remarkably observed as an increase in Ki-67 positive cells. The cell number of hNPCs was significantly increased after BDNF treatment represented by cellular metabolic activity of the cells measured by MTT assay. This noticeable effect was statistically shown at 20 ng/ml of BDNF treatment. BDNF, however, did not promote neurite outgrowth but increased neuronal cell number. It was found that AG490 suppressed hNPCs proliferation. However, this inhibitor partially decreased BDNF-induced hNPCs proliferation. These results demonstrated the potential role of BDNF for the amelioration of AD through the increase of AD-derived hNPCs number