Verbal Training Induces Enhanced Functional Connectivity in Japanese Healthy Elderly Population.

This study employs fMRI to examine the neural substrates of response to cognitive training in healthy old adults. Twenty Japanese healthy elders participated in a 4-week program and practiced a verbal articulation task on a daily basis. Functional connectivity analysis revealed that in comparison to age- and education-matched controls, elders who received the cognitive training demonstrated increased connectivity in the frontotemporal regions related with language and memory functions and showed significant correlations between the behavioral change in a linguistic task and connectivity in regions for goal-oriented persistence and lexical processing. The increased hippocampal connectivity was consistent with previous research showing efficacious memory improvement and change in hippocampal functioning. Moreover, the increased intra-network connectivity following cognitive training suggested an improved neural differentiation, in contrast to the inter-network activation pattern typical in the aging brain. This research not only validates the relationship of functional change in the frontal and temporal lobes to age-associated cognitive decline but also shows promise in turning neural change toward the right direction by cognitive training.

Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression.

Nicotine in tobacco smoke is considered carcinogenic in several malignancies including lung cancer. The high incidence of lung adenocarcinoma (LAC) in non-smokers, however, remains unexplained. Although LAC has long been less associated with smoking behavior based on previous epidemiological correlation studies, the effect of environmental smoke contributing to low-dose nicotine exposure in non-smoking population could be underestimated. Here we provide experimental evidence of how low-dose nicotine promotes LAC growth in vitro and in vivo. Screening of nicotinic acetylcholine receptor subunits in lung cancer cell lines demonstrated a particularly high expression level of nicotinic acetylcholine receptor subunit α5 (α 5-nAChR) in LAC cell lines. Clinical specimen analysis revealed up-regulation of α 5-nAChR in LAC tumor tissues compared to non-tumor counterparts. In LAC cell lines α 5-nAChR interacts with epidermal growth factor receptor (EGFR), positively regulates EGFR pathway, enhances the expression of epithelial-mesenchymal transition markers, and is essential for low-dose nicotine-induced EGFR phosphorylation. Functionally, low-dose nicotine requires α 5-nAChR to enhance cell migration, invasion, and proliferation. Knockdown of α 5-nAChR inhibits the xenograft tumor growth of LAC. Clinical analysis indicated that high level of tumor α 5-nAChR is correlated with poor survival rates of LAC patients, particularly in those expressing wild-type EGFR. Our data identified α 5-nAChR as an essential mediator for low-dose nicotine-dependent LAC progression possibly through signaling crosstalk with EGFR, supporting the involvement of environmental smoke in tumor progression in LAC patients.