期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms24097709
关键词
cAMP response element-binding protein (CREB); extracellular signal-regulated kinase (ERK); histone deacetylases; neurofilament light subunit (NF-L); ventrolateral orbital cortex
Neurofilament light chain (NF-L) plays a critical role in synapses relevant to neuropsychiatric diseases. The histone deacetylase inhibitor Trichostatin A (TSA) attenuated chronic morphine-induced behavioral sensitization and blocked the decrease of NF-L. The microinjection of TSA also blocked the increase of p-ERK/p-CREB/p-NF-L. These findings provide correlational evidence of NF-L involvement in opiate addiction.
Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.
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