The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1

Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential

“…Caspase activity was measured using the Caspase-Glo assay system (Promega, UK) as previously reported [23]. Briefly, breast cancer cell lines were seeded in 96-well plates at a density of 1 x 10 4 cells per well, allowed to attach overnight, serum-starved for 24 hours, and then exposed to test chemicals (± specific caspase inhibitor) as required.…”

Pharmacogenetics of Lithium Long-Term Treatment: Focus on Initiation and Adaptation Mechanisms

“…This is of relevance because the disruption of the glutamate balance is thought to be pivotal to the genesis of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, and, putatively, schizophrenia [78][79][80] . Consistent with this, one of the genes that was found to be overexpressed after lithium treatment in the formerly cited experiment conducted by Plant et al [44] was the Rho guanine nucleotide exchange factor 12: this enzyme has recently been demonstrated to modulate the vesicular traffic; its overexpression was found to result in enhanced secretion from immature granules, depleting cells of secretory cargos [81] . Even though the refined mechanism by which this depletion that could be triggered by chronic lithium treatment interacts with the monoamine balance or with the neuronal crosstalking in general is still far from being understood, this piece of evidence suggests that lithium activity may be a modulator of the neurotransmitter release.…”

“…The relevance of the PCK and of the MAPK pathways has been demonstrated in an elegant expression study on animals [35] . Other investigations reported results that are only partially overlapping: Plant et al [44] described the alteration of the expression profile of a set of genes in a neuronal blastoma line (14 statistically significant changes in expression after lithium exposure) and showed that a protein related to the antiapoptotic mechanism referred to as Six 1 was found to have a 31.3-fold increased expression after lithium exposure. Six 1 inhibits the apoptotic mechanism through the blockade of caspase 3 activation, thus further stressing the relevance of the neuroprotective activity of lithium.…”

Can a systems approach produce a better understanding of mood disorders?

“…Studies on their mode-of-action should, therefore, provide insight into the biological mechanisms of both normal and abnormal mood phenotypes. There have been many studies to examine the transcriptome impact of affective disorder treatments, most commonly lithium and valproate [84][85][86]. In addition, an increasing number of studies are looking at other levels of global organisation, such as the epigenome [87,88], proteome [89,90], phosphoproteome [91], and the metabolome [92].…”

“…This approach looks for commonalities in biological networks activated by multiple mood stabilising drugs, presuming these represent core biological hubs associated with affective disorders. A number of studies have been undertaken to compare mood stabilising drugs, most commonly lithium and valproate [84,86,93]. While the data from this approach is still emerging, it does seem to highlight programmed cell death as a common feature, consistent with an alteration in neural plasticity [94].…”