From the Cover: Arsenic Induces Hippocampal Neuronal Apoptosis and Cognitive Impairments via an Up-Regulated BMP2/Smad-Dependent Reduced BDNF/TrkB Signaling in Rats.
作者： Rukmani Pandey , Vipin Rai , Juhi Mishra , Kapil Mandrah , Somendu Kumar Roy
关键词:
摘要: Arsenic promotes hippocampal neuronal damage inducing cognitive impairments. However, mechanism arbitrating arsenic-mediated deficits remains less-known. Here, we identified that chronic exposure to environmentally relevant doses of arsenic increased apoptosis, characterized by caspase-3 activation, poly(ADP-ribose) polymerase cleavage and Terminal deoxynucleotidyl transferase dUTP nick-end labeling rat neurons, marked NeuN. Investigating apoptotic through invivo invitro studies revealed promoted bone morphogenetic protein-2 (BMP2) expression, supported BMP-receptor2 (BMPR2) p-Smad1/5 in neurons. BMP2-silencing treatment with BMP antagonist, noggin, attenuated the arsenic-induced apoptosis loss We then investigated whether BMP2/Smad signaling stimulated independently or required other intermediate pathways. hypothesized participation brain-derived neurotrophic factor (BDNF) survival. an attenuation BDNF-dependent TrkB signaling, observed co-treatment recombinant-BDNF reinstated BDNF/TrkB reduced apoptosis. To probe pathways could be linked, co-treated noggin recombinant BDNF. detected a noggin-mediated restored BDNF/TrkB, while failed affect signaling. In addition, found TrkB-inhibitor, K252a, nullified noggin-induced protection, proving necessity downstream BDNF/TrKB for BMP2/Smad-mediated arsenic-treated further related our observations performances, restoration transfer latency time learning-memory ability passive avoidance Y-Maze tests respectively rats. Overall, study proves up-regulated BMP2/Smad-dependent pathway, deficits.
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