Research Highlight: Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice

Salvatore Lecca and ENP Team leader Manuel Mameli led a study that identified early cellular changes necessary to trigger depressive symptoms, and a novel target that may have potential therapeutical relevance for mood disorders.

They found that the activity of neurons located in the lateral habenula - a nucleus fundamental for aversion and disappointment – increased after a stressful experience. This occurred via a reduced function of two membrane proteins (i.e. GABAB and GIRK2), which are necessary in controlling neuronal activity. As a consequence these modifications led to behavioral phenotype typical of depressive states.

Using a variety of electrophysiological, viral-based and pharmacological approaches the scientists were able to identify the cellular mechanisms underlying the negative experience, and to design a rescue strategy by targeting a specific phosphatase (PP2A). Inhibition of PP2A efficiently ameliorates depressive phenotypes in mouse models of mood disorders.

These results provided a detailed mechanistic picture of the events occurring upon a stressful stimuli highlighting the role of the lateral habenula in the aetiology of depression and providing new insights for the treatment of mood disorders.

Check out the article:

Lecca S, Pelosi A, Tchenio A, Moutkine I, Lujan R, Hervé D, Mameli M. Rescue of GABAB and GIRK function in the lateral habenula by protein phosphatase 2A inhibition ameliorates depression-like phenotypes in mice. Nat Med. 2016 Jan 25.

Doi: 10.1038/nm.4037. [Epub ahead of print]

Keywords: Lateral habenula, depression, GABAb-GIRK