Neuroactive steroids (NS) protect our nervous systems, promote the growth of new nerve cells and protect our nerve cells from apoptosis. NS are altered in people with bipolar disorder. The authors theorized that the drug Valproate and lithium could prevent apoptosis and that drugs used for manic-depressive disorder might work by increasing levels of NS.
Two NS chemicals are allopregnanolone and pregnenolone. Allopregnanolone is synthesized from cholesterol and at nanomolar levels, allopregnanolone increases GABA A receptor activity. It reduces anxiety, is anticonvulsant and protects cells from apoptosis. Pregnenolone metabolizes into allopregnanolone.
Rats were tested to see if treatment with lithium or Valproate altered brain levels of allopregnanolone or pregnenolone. Chronic use of lithium was shown to result in increased levels of allopregnanolone in the rat anterior brain cortex. The study showed that allopregnanolone was tripled in the brains of lithium-treated mice and slightly increases pregnenolone levels in the brain. Valproate treatment did not increase allolpregnanolone or pregnenolone levels.
Lithium treatments reduce the risk of suicide and the author believes this could be due to increased NS levels.
CONCLUSION: Increased levels of NS may be one of the mechanisms by which lithium works and is neuroprotective. The author believes that this conclusion is supported by present data. The NS increase results in increased neurogenesis (the production of new brain tissue) and the proliferation of stem cells.
NOTE: Valproate is pharmaceutical and requires a prescription.
Lithium treatment has been shown to increase the gray matter of the mouse brain by 3% with chronic treatment. Many studies have shown lithium to be neuroprotective and capable of stimulating the growth of new brain tissue.
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