HDAC6 Modulates Amyloid β-Induced Hippocampal Neurons Function and Morphology by Regulating HSP90
LIU Zhen1, HAO Kaimin1, QI Wenxiu2*
The aim of this study was to investigate the effect of HDAC6 (histone deacetyltase 6) on the functional and morphology of the Aβ (amyloid beta)-induced primary hippocampal neurons by regulating HSP90. In vitro primary culture was conducted on the hippocampal neurons of 18 days pregnant SD rats, the purity of hippocampal neurons was identified with β-tubulin III antibody after 7 days. After oligomeric-Aβ1-42 (oligomericamyloid beta peptides 1-42) cultured 24 hours, a variety of drugs including HDAC6 inhibitor TSA (tubastatin A hydrochbride), HDAC6 agonist Theo (theophylline), HSP90 inhibitor Gane (ganetespi), or saline (Aβ+NS group) were added and then cultured 24 h, Saline group as a control (NS group). Then cell viability was detected by CCK8 assay, the length and branchs of neurons were used with immunofluorescence staining, the levels of HDAC6 and HSP90 protein were detected by Western blot, and the mRNA expressions of hsp90 were performed to use qRTPCR (quantitative Real-time polymerase chain reaction). The results showed that HDAC6 hibitor could not only down-regulate the level of HDAC6 and promote the expressions of hsp90 mRNA and HSP90 protein, but also could increase the activity of hippocampal neurons, the length of protuberances and the number of branches. However, there appeared to be an opposite effect in the agonist of HDAC6. Moreover, the cell viability, synaptic length and number of branches after the application of HSP90 inhibitor were decreased, but no significant changes in the level of HDAC6. Thus, we speculate that HDAC6 may influence the functional and morphology of the Aβ-induced primary hippocampal neurons by regulating HSP90 levels.
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