An Oldie but Goodie: Lithium in the Treatment of Bipolar Disorder through Neuroprotective and Neurotrophic Mechanisms

Abstract

Lithium has been used for the treatment of bipolar disorder (BD) for the last sixty or more years, and recent studies with more reliable designs and updated guidelines have recommended lithium to be the treatment of choice for acute manic, mixed and depressive episodes of BD, along with long-term prophylaxis. Lithium’s specific mechanism of action in mood regulation is progressively being clarified, such as the direct inhibition on glycogen synthase kinase 3β, and its various effects on neurotrophic factors, neurotransmitters, oxidative metabolism, apoptosis, second messenger systems, and biological systems are also being revealed. Furthermore, lithium has been proposed to exert its treatment effects through mechanisms associated with neuronal plasticity. In this review, we have overviewed the clinical aspects of lithium use for BD, and have focused on the neuroprotective and neurotrophic effects of lithium.

Contrasting effects of chronic lithium, haloperidol and olanzapine exposure on synaptic clusters in the rat prefrontal cortex

“…The increase in NLGN cluster count and area upon Li treatment is consistent with the reported neurotrophic effects of this drug, although the mechanisms underlying this effect are as yet poorly understood 27 . At the resolution of our data we are unable to say whether the increase in NLGN clusters is due to an increase in the number of postsynaptic specialisations (such as increased spine density), or whether an increase in the size of pre-existing clusters due to postsynaptic protein accumulation 24 leads to inclusion of clusters that were previously below detection level.…”

“…To gain further insight into the effect of psychotropic medication on synaptic density, we therefore investigated the effects of HAL, OLZ, and Li treatments on SV2A and Neuroligin (NLGN) clusters as global pre-and postsynaptic marker, respectively. We hypothesised that cluster count would be unaffected by chronic exposure to either HAL or OLZ, concurrent with our earlier data 19 , however we anticipated that chronic exposure to Li, which has been suggested to have neurotrophic and neuroprotective effects 21,27 , would lead to an increase in synaptic clusters. Our research provides one of the first investigations into the effect of these different psychotropic medications on SV2A clusters.…”

Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication

“…The anti-depressant drug lithium is a well-known Food and Drug Administration-approved drug for nearly 60 years. Accumulating evidence suggests that LiCl have diversity of functions on physiological and pathological processes, including cancerogenic or anti-cancerogenic properties, immune-stimulatory and immunosuppressive functions [6,7].…”

“…So LiCl has been explored for treating diabetes, Alzheimer's disease and ovarian cancer, as well as antimicrobial infection [7]. Prior investigations have also revealed that LiCl exhibits antiviral effects on certain viruses, e.g., coronavirus, herpes simplex, infectious bronchitis virus, porcine reproductive and respiratory syndrome (PRRS) and feline calicivirus [8][9][10][11][12][13][14][15].…”

The role of lithium in the treatment of bipolar disorder

“…The role of lithium in the treatment of bipolar disorder D Ariyasinghe, SR Perera Snips from the journals An oldie but goodie: Lithium in the treatment of bipolar disorder through neuroprotective and neurotrophic mechanisms (1) The exact mechanism whereby lithium exerts its therapeutic effects is still unclear. This review article focuses on the use of lithium in bipolar disorder, as well as highlighting the neuroprotective and the neurotrophic effects of lithium.…”