Down syndrome (DS), caused by trisomy 21, is characterized by intellectual disability and accelerated aging, with chronic oxidative stress contributing to neurological deficits. REST (Repressor Element-1 Silencing Transcription factor), a crucial regulator of neuronal gene expression implicated in DS neuropathology. This study investigates the neuroprotective potential of lithium, a mood stabilizer with known cognitive-enhancing effects, in restoring levels of REST. Using three pairs of human disomic and trisomic DS induced pluripotent stem cell (iPSC) isogenic lines, we differentiated neurons and treated them with lithium. Nuclear REST expression and reactive oxygen species (ROS) levels were quantified. Results showed the significantly lower nuclear REST expression in DS neurons was restored after 24 h of 10 mM lithium carbonate treatment. Notably, lithium treatment selectively reduced ROS levels in DS neurons to near-baseline levels. When challenged with hydrogen peroxide, DS neurons exhibited increased vulnerability to oxidative stress. The lithium treatment also significantly reduced ROS levels in the stressed control neurons. These findings reveal a positive association between lithium treatment, REST restoration, and oxidative stress reduction, suggesting that repurposing lithium could contribute to developing therapeutic strategies for DS neuropathologies. This study provides novel insights into DS molecular mechanisms and highlights the potential of lithium as a targeted intervention for improving neuronal function in DS.
Inspite of the advent of newer antimanic drugs, lithium carbonate remains widely used in the treatment and prevention of manic-depressive illness. However care has to be exercised due to its low therapeutic index. The central nervous system and renal system are predominantly affected in acute lithium intoxication and is potentially lethal. The more common side effect involves the central nervous system. It occurs early and is preventable. We describe three cases of lithium toxicity admitted to Johor Bahru Hospital, with emphasis on its neurological preponderance.
Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression, and prophylaxis of bipolar disorders. Thyroid abnormalities have been associated with treatment with lithium. Zinc is an essential trace element that plays a role in several biological activities. Therefore, the present study was aimed at investigating the potential role of zinc in the thyroid gland following lithium administration to explore the role of zinc under such conditions. To achieve this goal, male Wistar rats (150-195 g) were divided into four groups: Group 1 animals were fed standard pellet feed and tap water ad lib; Group 2 rats were fed lithium in the form of lithium carbonate through diet at a concentration of 1.1 g/kg body weight; Group 3 animals received zinc treatment in the form of zinc sulfate (ZnSO4·7H2O) at a dose level of 227 mg/L mixed with drinking water of the animals; and Group 4 animals were given lithium and zinc in a similar manner as was given to the animals belonging to groups 2 and 4 respectively. The role of zinc on thyroid functions in lithium-treated rats was studied after 2, 4, and 8 weeks of different treatments. Zinc has been observed to have the capability to nearly normalize the altered 2-h uptake of 131I, biological and effective half-lives of 131I, and circulating T4 levels that were altered after lithium treatment. The present study concludes that zinc may be an effective agent in normalizing the adverse effects caused by lithium on thyroid functions.