Regional changes in purines and selected purinergic receptors in immature rat brain exposed to lead

Lead (Pb) toxicity still remains a significant health problem, since it was recognized as a potent neurodevelopmental toxin. Regarding the fact that in the nervous system ATP is not only the energy source but also acts as a signaling molecule outside the cell, it was of interest to investigate both the level of purines and expression of purinergic receptors in different regions of immature rat brain under Pb toxicity conditions. We examined the expression of A(1) receptor which is involved in neuroprotective mechanisms, and P2X(7)R receptor related to the inflammatory and neurodegenerative processes. Expression of receptors' protein was analysed using immunoblotting method whereas HPLC method was used to measure the levels of purines. We observed the features of energetic stress in all examined brain structures expressed by decrease in ATP and ADP levels and AEC ratio. However, in forebrain cortex, the observed changes were milder than in cerebellum and hippocampus. Enhanced expression of AIR and high increase of adenosine (Ado) level, suggest the proper function of protective mechanisms mediated by Ado. We have found that hippocampus is most vulnerable to Pb toxicity, both due to the high energy depletion and the pattern of expression of investigated receptors. Enhanced expression of P2X(7)R and connexin 43 (Cx43) in glial fraction (GPV), suggests the involvement of astrocytic pool of cells into the pathological changes observed in this structure of Pb-exposed immature rat brains. (C) 2010 Elsevier Ireland Ltd. All rights reserved.