Upregulation of GABAA-receptor alpha1- and alpha2-subunit mRNAs following ischemic cortical lesions in rats

Abstract

Focal cortical lesions are associated with a functional downregulation of the GABAergic system in perilesional tissue lasting (at least) several weeks. The molecular mechanisms underlying this phenomenon are still poorly understood. Here we used RT-PCR to investigate whether mRNA-levels of two alpha-subunits of the GABAA-receptor (alpha1- and alpha2-subunits) change following ischemic cortical lesioning. The results show that 7 days after lesion induction mRNA-levels for both the alpha1- and alpha2-subunits are increased threefold in perilesional tissue ipsilateral, but not contralateral to the lesion. Taken together with the results of a previous immunohistochemical study in which a moderate decrease of the alpha1-subunit-protein and no change for the alpha2-subunit [T. Neumann-Haefelin, J.F. Staiger, C. Redecker, K. Zilles, J.M. Fritschy, H. Mohler, O.W. Witte, Immunohistochemical evidence for dysregulation of the GABAergic system ipsilateral to photochemically induced cortical infarcts in rats. Neuroscience (Oxford) 87 (4) (1998) 871-879] was observed, this is interpreted as a partial block of translation in the perilesional tissue surrounding cortical ischemic lesions.