Smoking cessation is crucial for patients with coronary heart disease (CHD), yet depression may impede cessation success. We systematically reviewed the prospective association between depression and subsequent smoking cessation in individuals with CHD to quantify this effect. Electronic databases (PsychInfo, PubMed, CINAHL) were searched for prospective studies of patients with CHD that measured depression at baseline (scales, diagnostic interview, or antidepressant prescription) and reported smoking continuation/cessation at follow-up. Inclusive dates were January 1, 1990, to May 22, 2013. Standardized mean differences (SMDs) and associated 95% confidence intervals were estimated using random-effects meta-analysis. Sensitivity analysis explored the impact of limiting meta-analysis to studies using different depression measures (validated scales, diagnostic interviews, antidepressant prescription), different durations of follow-up, or higher-quality studies. From 1185 citations retrieved, 28 relevant articles were identified. Meta-analysis of all available data from 20 unique data sets found that depressed patients with CHD were significantly less likely to quit smoking at follow-up (SMD = -0.39, 95% confidence interval = -0.50 to -0.29; I(2) = 51.2%, p = .005). Estimates remained largely unchanged for each sensitivity analysis, except for two studies that used antidepressants, which showed a much larger effect (SMD = -0.94, -1.38 to -0.51; I(2) = 57.7%, p = .124). Patients with CHD and depressive symptoms are significantly less likely to quit smoking than their nondepressed counterparts. This may have implications for cardiovascular prognosis, and CHD smokers may require aggressive depression treatment to enhance their chances of quitting.

Mechanical properties of the brain such as intracranial pressure or stiffness of the matrix play an important role in the brain’s normal physiology and pathophysiology. The physical properties are sensed by the cells through mechanoreceptors and translated into ion currents which activate multiple biochemical cascades allowing the cells to adapt and respond to changes in their microenvironment. Piezo1 is one of the first identified mechanoreceptors. It modulates various central nervous system functions such as axonal growth or activation of astrocytes. Piezo1 signaling was also shown to play a role in the pathophysiology of Alzheimer’s disease. Here, we explore the expression of the mechanoreceptor Piezo1 in human MO3.13 oligodendrocytes and human MS/non-MS patients’ brains and investigate its putative effects on oligodendrocyte proliferation, maturation, and migration. We found that Piezo1 is expressed in human oligodendrocytes and oligodendrocyte progenitor cells in the human brain and that its inhibition with GsMTx4 leads to an increment in proliferation and migration of MO3.13 oligodendrocytes. Activation of Piezo1 with Yoda-1 induced opposite effects. Further, we observed that expression of Piezo1 decreased with MO3.13 maturation in vitro. Differences in expression were also observed between healthy and multiple sclerosis brains. Remarkably, the data showed significantly lower expression of Piezo1 in the white matter in multiple sclerosis brains compared to its expression in the white matter in healthy controls. There were no differences in Piezo1 expression between the white matter plaque and healthy-appearing white matter in the multiple sclerosis brain. Taken together, we here show that Piezo1-induced signaling can be used to modulate oligodendrocyte function and that it may be an important player in the pathophysiology of multiple sclerosis.

The sphingosine 1-phosphate receptor subtype 1 (S1P1R) is modulated by phosphorylated FTY720 (pFTY720), which causes S1P1R internalization preventing lymphocyte migration thus limiting autoimmune response. Studies indicate that internalized S1P1Rs continue to signal, maintaining an inhibition of cAMP, thus raising question whether the effects of pFTY720 are due to transient initial agonism, functional antagonism and/or continued signalling. To further investigate this, the current study first determined if continued S1P1R activation is pathway specific. Using human and rat astrocyte cultures, the effects of S1P1R activation on cAMP, pERK and Ca(2+) signalling was investigated. In addition, to examine the role of S1P1R redistribution on these events, a novel biologic (MNP301) that prevented pFTY720-mediated S1P1R redistribution was engineered. The data showed that pFTY720 induced long-lasting S1P1R redistribution and continued cAMP signalling in rat astrocytes. In contrast, pFTY720 induced a transient increase of Ca(2+) in astrocytes and subsequent antagonism of Ca(2+) signalling. Notably, while leaving pFTY720-induced cAMP signalling intact, the novel MNP301 peptide attenuated S1P1R-mediated Ca(2+) and pERK signalling in cultured rat astrocytes. These findings suggested that pFTY720 causes continued cAMP signalling that is not dependent on S1P1R redistribution and induces functional antagonism of Ca(2+) signalling after transient stimulation. To our knowledge, this is the first report demonstrating that pFTY720 causes continued signalling in one pathway (cAMP) versus functional antagonism of another pathway (Ca(2+)) and which also suggests that redistributed S1P1Rs may have differing signalling properties from those expressed at the surface.