Lithium has the simplest structure of any therapeutic agent and its bioactive properties have been known for over a century. However, the basis of its clinical use as an anti-depressant is still unclear. Furthermore, lithium treatment has potentially serious side-effects. An understanding of the molecular mechanisms of lithium action may shed light on the biological basis for depression and the causes of its side-effects.

Drs Adrian Harwood, Robin Williams, Anne Mudge and Lili Cheng are researchers at the MRC Laboratory of Molecular Cell Biology, University College London. They are trying to understand how anti-manic function. To define the effect of these , they have been using both Dictyostelium discoideum, a cellular slime mould, and primary rat Dorsal root ganglia neurons (pictured).

The images shown here were captured using one of the many Openlab cell imaging systems installed in the LCMB. The cells are primary neurons double-labeled for actin (fluorescent Alexa 594- phalloidin, shown as green) and acetylated tubulin (labeled with Texas Red). The images show the axonal network containing acetylated tubulin and the growth cone with actin structures.

They have found that lithium has numerous effects on developing neurons including enlarging the size of the growth cone and causing abnormal microtubule extension into the growth cone. This can be clearly seen in these images. The change in size can be reversed by inositol, which suggests that lithium affects inositol signaling pathways. The enlargement can also be reversed by inhibitors to prolyl oligopeptidase, an enzyme known to be regulated differently in patients with manic