DEVELOPMENTAL EXPRESSION OF CALCIUM-BINDING PROTEIN-CONTAINING NEURONS IN NEOCORTICAL TRANSPLANTS

The present study examined the development of calcium binding protein- containing neurons in a timed series of fetal neocortical transplants, The immunoexpression of parvalbumin and calbindin, which are subpopul ations of GABAergic neurons, have been widely studied in normal develo pment and in disease and injury states, Because of their purported res istance to oxidative injury by their ability to buffer Ca++ influx, th ese neurons have been particularly studied following ischemia. Because it is likely that oxidative stress is associated with the grafting pr ocedure, we sought to determine if these neurons displayed enhanced su rvival characteristics, Normally, parvalbumin and calbindin represent about 5-10% of cortical neurons, Within 2-4 wk after grafting the expr ession of both proteins increased markedly in that a relatively larger number of neurons (27% for parvalbumin) were immunopositive, This inc rease was transitory, however, and by 4 mo and beyond, confocal micros copic data showed a reduction of over 50% of parvalbumin (+) neurons a nd processes, Calbindin (+) processes showed a qualitative change in t hat they were smaller with less terminal branching, Electron microscop y confirmed a substantial reduction in parvalbumin synaptic contacts, Interestingly, in older grafts, remaining parvalbumin neurons were tho se that were strongly NSE (+) suggesting a link between normal metabol ism and Ca++ buffering in grafted neurons, It is possible that in earl y grafts certain neuronal populations transiently upregulated calcium binding proteins as a defensive mechanism against Ca++ influx associat ed with oxidative stress, Over time, however, following physiological normalization within grafts, the calcium binding protein (+) neurons a re diminished, possibly due to lack of appropriate afferent input to t he interneuronal pool. (C) 1998 Elsevier Science Inc.