Uncoupling protein 2 in the brain: distribution and function.

Uncoupling protein 2 (UCP2) mRNA is expressed in a panoply of tissues, including the brain, where it is widely distributed. In the mouse brain, it is expressed in the hypothalamus (suprachiasmatic, paraventricular, dorsomedial, ventromedial and arcuate nuclei), the thalamus (submedius nucleus) and the brain-stem (dorsal motor nucleus of the vagus nerve). In the rat brain, it is also expressed in the hippocampus. The presence of UCP2 mRNA in neurons expressing corticotropin-releasing factor and arginine-vasopressin suggests a role for UCP2 in the control of neuroendocrine and behavioural functions. We have recently demonstrated that UCP2-deficient mice can resist the lethal effect of toxoplasmosis through an enhanced production of reactive oxygen species (ROS) from the macrophages. This finding provides evidence that UCP2 can be part of a mechanism preventing ROS production. UCP2 could therefore be involved in protecting the brain against oxidative stress. The involvement of UCP2 in neuroprotection is also consistent with the recent observation that kainic acid, which promotes Ca(2+) uptake in the glutamate-activated neurons in the hippocampal CA1 field, can induce the UCP2 gene in the activated CA1 cells. The role of UCP2 in neuroprotection warrants further investigation.