Arches. Photo by Daniel Chia
HOPES: Huntington's Outreach Project for Education, at Stanford
Aug
21
2012

Lithium

Background^

Lithium is a soft, light metal that is used in various industries, including in the production of ceramics, glass, and batteries. It is found in trace amounts in all living organisms. While it is not necessary for survival, lithium does play some role in the human body since the lithium ion (Li+ ) has neurological effects. In medicine, Li+ is used to treat psychiatric disorders, specifically to stabilize mood and treat mania symptoms of bipolar disorder, a mood disorder characterized by alternating episodes of depression and mania.

The method by which lithium affects the brain to influence mood remains unclear but several mechanisms have been suggested. Scientists believe that lithium could stabilize mood by regulating levels of glutamate, the main excitatory neurotransmitter in the brain (For more on glutamate, click here.), or by interacting with nitric oxide, a gaseous signaling molecule. It could also work by altering the body’s circadian rhythm (biological clock).

HD and Lithium^

In recent years, researchers have investigated lithium as a potential treatment for HD because of its ability to regulate glutamate levels. Several studies have evaluated the effects of lithium on rat models of HD.

In the Wei et al. (2001) study, rats were injected with a lithium solution or with a control saline solution daily. After 16 days, the researchers infused the rats’ brains with quinolinic acid (QA), a chemical that has neurotoxic effects and is an agonist that activates the glutamate NMDA receptors. QA injections produce rats with lesions that lead to HD-like symptoms because one potential cause of HD pathology is over-activation of NMDA receptors due to high concentrations of glutamate. This over-activation can cause neuron death. Results showed that the brains of rats that received pre-treatment with lithium contained significantly smaller lesions (40-50%) than those treated with the control solution. Since lithium inhibits excessive NMDA receptor function, it could potentially counteract over-activation of NMDA receptors that occurs in the HD brain (For more on NMDA receptors and its role in HD, click here.). Nevertheless, it remains unclear how long the rats must be treated with lithium in order to sustain these positive effects. Future studies need to be conducted to answer this question.

Another study by Senatorov et al. (2004) used a similar QA-infused rat model of HD but instead injected rats with either lithium or saline control twice, once 24 hours prior to, and 1 hour after, QA infusion. Seven days later, lithium treatment again decreased lesions by 40% as compared to the control. In addition to its role in preventing neuronal death, the researchers believe lithium also has ability to produce new neurons in the hippocampus, a brain area involved in learning and memory.

Side Effects^

Lithium has numerous side effects and can be toxic at high doses. The most common side effects are nausea, headaches, and hand tremor. Because lithium is a salt, it can also cause electrolyte imbalance and dehydration.

Conclusion^

Research on lithium and HD is still in its early stages, as studies with HD patients have yet to be conducted. However, research on lithium in rat models of HD has yielded promising results so far.

For further reading:^

1. Wei et al. “Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington’s disease.” Neuroscience, Volume 106, Issue 3, 27 September 2001, Pages 603-612.

2. Senatorov et al. “Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington’s disease.” Molecular Psychiatry (2004) 9, 371–385.

- A. Zhang, 08-21-12