Two major enzymatic pathways, the PI and GSK3, are altered by lithium, and magnesium displacement might be a common mechanism of action, although the precise contribution of each to clinical effects is uncertain. The effects of these pathways and their downstream effects offer tantalising, incomplete, evidence for how lithium might exert clinical effects. Altered autophagy could provide cognitive [Caccamo et al. 2010], neuroprotective [Chiu and Chuang 2010] and mood stabilisation [Cleary et al. 2008]. Cytoskeletal growth stabilisation and plasticity appear to lead to

Inhibitors,research,lifescience,medical stabilisation of aberrant neuronal activity, a conceptually attractive target for a mood-stabilising drug [Lenox and Watson, 1994]. Decreased dopamine release following chronic treatment has been suggested as a viable, at least partial, Inhibitors,research,lifescience,medical explanation for lithium’s mood-stabilising action [Ferrie et al. 2006] and effects on glutamate receptor functions through GSK3 inhibition may preserve and enhance both LTP and LTD [Peineau et al. 2007], with potential effects on learning and memory, which can be adversely affected in affective disorders, as well as neurodegenerative disorders. Alteration of intracellular calcium homeostasis

has been identified in mood disorders, and downstream regulation of calcium signalling following lithium [Sourial-Bassillious et al. 2009] offers another potential therapeutic mechanism [Bauer et al. 2003a; Wasserman et Inhibitors,research,lifescience,medical al. 2004; Perova et al. 2008]. Similarly alterations in sleep patterns are a clinically long recognised precipitant and symptom of mood disturbances: most therapeutic work in this regard has explored monoaminergic effects on the thalamus, but there is now evidence for lithium modulating circadian patterns Inhibitors,research,lifescience,medical and suprachiasmatic nuclear functioning and expression of clock genes. Lithium’s Inhibitors,research,lifescience,medical evidenced ability to prevent or partly reverse the grey-matter deficits seen in bipolar patients [Sassi et al. 2002] has also been linked to specific therapeutic effects,

including its effects on http://www.selleckchem.com/products/Temsirolimus.html suicidality, potentially through impacting on goal directed behaviour and affecting cognitive distortions [Benedetti et al. 2011]. Further work is required to better elucidate the mechanism of action of this effective, but potentially toxic, drug. Understanding which processes contribute to clinical improvement, and how, affords at least the potential many to develop targeted compounds, although undoubtedly the challenges faced in so doing are enormous. Better knowledge of the neuropathophysiology will also enhance our understanding of the neuroscience of affective disorders and potentially neurodegenerative conditions. Acknowledgments The authors are grateful to Dr Richard McQuade, Psychobiology Research Group, Institute of Neuroscience, Newcastle University, for email correspondence and discussion of his on-going work in this field that helped with the preparation of the final draft of this manuscript.