Lithium enhances neuronal resilience and hampers long-term neuronal (and by extension, mental) deterioration. Its mood stabilising properties are due to multi-level actions on the intracellular signal transduction pathways affecting the function of G proteins, of some intracellular messengers (mio-inositol, MARKS, Bcl-2, ER stress proteins, calmodulin-synapsin1-synaptotagmin complex), and of some key enzymes (adenilyl cyclase, protein kinases A, C? and C?, GSK-3, ERK, MAP-kinase). In the long run, mood-stabilising agents enhance blockade of excitotoxic/apoptotic pathways, phosphorylation and rearrangement of microtubular proteins, and regulation of the expression of genes implicated in processes involved in neuroplasticity, neuroprotection, even neurogenesis. Long-term stabilisation of mood has taught us the lesson that pharmacologic enhancement of neuroprotective/neurotrophic mechanisms carries a high promise for effective interventions not only in bipolar affective disorder and schizophrenia but in brain damage, dementias and other neurodegenerative diseases, and even in stress-induced mental disorders.
Keywords: lithium, bipolar disorder, signal transduction, neuroplasticity