Molecular mechanisms: Lithium treats adult fragile X symptoms

Treating adult mice with lithium restores the ability of neurons in fragile X mice to fine-tune their signaling, according to a study published online in November in Brain Research.

In a healthy brain, activation of synapses, the junctions between neurons, is often followed by a damping down of signals, also called long-term depression, or LTD. In mice with fragile X syndrome, LTD is particularly enhanced at synapses in the hippocampus, altering the fine-tuned regulation of the synapse — a process called synaptic plasticity.

Several promising treatments for fragile X syndrome target a family of proteins called mGluR. These proteins trigger a signaling cascade that regulates synaptic plasticity and induces LTD.

Lithium treatment has been shown to rescue social impairment in fruit flies and mice that model fragile X syndrome. A preliminary clinical trial has also shown some improvements in people with the disorder.

These previous studies involved short-term treatment with lithium, however. The new study is the first to look at the effects of chronic treatment with lithium in adult mice.

Researchers gave mice lithium in their food, beginning at 5 to 6 weeks of age and until the mice reached 9 to 12 months. Lithium restores LTD triggered by mGluR to normal levels in the hippocampi of fragile X mice, but does not affect controls.

Lithium given to 2-month-old adult mice for up to three months also restores LTD to normal levels, suggesting that it could improve fragile X symptoms in adults with the disorder.