Complex modulation of the expression of PKC isoforms in the rat brain during chronic type 1 diabetes mellitus

We previously demonstrated that chronic hyperglycemia has a detrimental influence on neurovascular coupling in the brain-an effect linked to an alteration in the protein kinase C (PKC)-mediated phosphorylation pattern. Moreover, the activity of PKC was increased, in diabetic rat brain, in a tissue fraction composed primarily of the superficial glia limitans and pial vessels, but trended toward a decrease in cerebral cortical gray matter. However, that study did not examine the expression patterns of PKC isoforms in the rat brain. Thus, in a rat model of streptozotocin (STZ)-induced chronic type 1 diabetes mellitus (T1DM), and in non-diabetic (ND) controls, two hypotheses were addressed. First, chronic T1DM is accompanied by changes in the expression of PKC-alpha, beta III, gamma, delta, and s Second, those changes differ when comparing cerebral cortex and glio-pial tissue. In addition, we analyzed the expression of a form of PKC-gamma, phosphorylated on threonine 514 (pT514-PKC-gamma), as well as the receptor for activated C ldnase 1 (RACK1). The expression pattern of different PKC isoforms was altered in a complex and tissue-specific manner during chronic hyperglycemia. Notably, in the gray matter, PKC-alpha expression significantly decreased, while pT514-PKC-gamma expression increased. However, PKC-beta II, -gamma, -delta, -epsilon, and RACK1 expressions did not change. Conversely, in glio-pial tissue, PKC-alpha and RACK1 were upregulated, whereas PKC-gamma, pT514-PKC-7, and PKC-epsilon were downregulated. PKC-beta II, and PKC-delta, were unchanged. These findings suggest that the PKC activity increase previously seen in the glio-pial tissue of diabetic rats may be due to the selective upregulation of PKC-alpha, and ultimately lead to the impairment of neurovascular coupling. (C) 2012 Elsevier B.V. All rights reserved.