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.

Background: Ethiopia is renowned for its pivotal role in the origin and evolution of humanity, with its rich hominid fossil records and unique geological features offering critical insights into early human development. However, genetic studies focusing on the structure and forensic characteristics of the Addis Ababa population in Ethiopia (AAE) remain sparse. Results: A total of 378 short tandem repeat (STR) alleles were observed in 605 unrelated individuals from the AAE, with allelic frequencies ranging from 0.0008 to 0.4678. All loci were in Hardy-Weinberg equilibrium. The SE33 locus exhibited the highest power of discrimination (PD = 0.993), while D22S1045 showed the lowest PD (0.86623). The combined power of discrimination (> 0.999999999), combined power of exclusion (> 0.999999999), and combined match probability (3.33707 × 10 ^− 19 ) of 24 STR loci, suggest that they are highly polymorphic and suitable for forensic individual identification and paternity testing. Furthermore, population genetic analysis revealed that the AAE had a closer relationship with African populations and affected by West Eurasian migration as well. Conclusions: Our findings showed that the 24 STR loci panel possessed high polymorphism, which could serve as a reference STR database for forensic applications and population genetics study for the AAE population.

Morphine addiction is driven in part by persistent reward-associated memory, yet the molecular mechanisms linking translational control to cellular stress responses remain unclear. In the present study, using a mouse morphine-induced conditioned place preference and N2a cell model, we investigated apoptosis-related alterations in the medial prefrontal cortex and the involvement of eIF4E-dependent translational regulation and BDNF/TrkB signaling. Morphine-induced conditioned place preference was associated with an increase in TUNEL-positive cells in the medial prefrontal cortex, accompanied by upregulation of Bax and downregulation of Bcl-2. In N2a cells, morphine induced apoptosis in a dose-dependent manner. Morphine also increased neuronal eIF4E expression in both mPFC tissue and N2a cells, accompanied by upregulation of BDNF and TrkB. Inhibition of the eIF4E/eIF4G interaction with 4EGI-1 significantly affected morphine-induced CPP formation and altered apoptosis-related markers and BDNF/TrkB expression. Notably, intra-mPFC administration of 4EGI-1 suppressed morphine-induced CPP without affecting anxiety-like behavior, locomotor activity, or general learning and memory performance. These findings suggest that eIF4E-dependent translational regulation is functionally associated with morphine-induced reward memory and apoptosis, potentially in association with changes in BDNF/TrkB molecular expression. This study offers novel insight into the molecular basis of morphine addiction and highlights a potentially targetable translational regulatory pathway for therapeutic intervention.