Differential Expression of PTEN in Normal Adult Rat Brain and Upregulation of PTEN and p‐Akt in the Ischemic Cerebral Cortex

Abstract

The tumor suppressor phosphatase and tensin homologue (PTEN) is a protein and lipid phosphatase. PTEN mutations have been associated with a large number of human cancers. To understand the physiological role of PTEN in the brain and its relationship to Akt in ischemic injury, we first investigated the localization of PTEN immunoreactivity in the brains of normal adult rats using immunohistochemistry. We then detected the modulation of PTEN and p-Akt following transient global ischemia by Western blot and immunohistochemistry analyses. Our observation of normal brains showed that PTEN was heterogeneously distributed in the cytoplasm, nuclei, and processes in different regions. It was shown immunohistochemically that PTEN was distributed differentially in rat brain, with the highest levels in the anterior olfactory nucleus, cerebral cortex, amygdaloid nucleus, hippocampus, Purkinje's cells, and several nuclei in the basal ganglia, thalamus, midbrain, and pons. After global cerebral ischemia, PTEN and p-Akt immunoreactivities were increased in the cerebral cortex. This was accompanied by the nuclear translocation of p-Akt. Double-labeling experiments revealed that PTEN and p-Akt were most likely localized to neurons. These results suggest a role for PTEN in normal adult brain and that the PTEN/Akt pathway may be involved in neuronal survival or plasticity after ischemic injury.