MERCURY-VAPOR INHALATION INHIBITS BINDING OF GTP TO TUBULIN IN RAT-BRAIN - SIMILARITY TO A MOLECULAR LESION IN ALZHEIMER-DISEASED BRAIN

Hg2+ interacts with brain tubulin and disassembles microtubules that m aintain neurite structure. Since it is well known that Hg vapor (Hg-0) is continuously released from ''silver'' amalgam tooth fillings and i s absorbed into brain, rats were exposed to Hg-0 4 h/day for 0,2,7, 14 and 28 d at 250 or 300 mu g Hg/m(3) air, concentrations present in mo uth air of some humans with many amalgam fillings. Average rat brain H g concentrations increased significantly (11-47 fold) with duration of HgO exposure. By 14 d Hg-0 exposure, photoaffinity labelling of the b eta-subunit of the tubulin dimer with [alpha(32)P]8N(3)GTP in brain ho mogenates was decreased 41-74%, upon analysis of SDS-PAGE autoradiogra ms. The identical neurochemical lesion of similar or greater magnitude is evident in Alzheimer brain homogenates from approximately 80% of p atients, when compared to human age-matched neurological controls. Tot al tubulin protein levels remained relatively unchanged between Hg-0 e xposed rat brains and controls, and between Alzheimer brains and contr ols. Since the rate of tubulin polymerization is dependent upon bindin g of GTP to tubulin dimers, we conclude that chronic inhalation of low -level Hg-0 can inhibit polymerization of brain tubulin essential for formation of microtubules. (C) 1997 Inter Press, Inc.