Calbindin-D 28k Immunoreactivity within the Cholinergic and GABAergic Projection Neurons of the Basal Forebrain

Abstract

The purpose of this study was to determine whether the calcium binding protein calbindin-D 28k was present within the cortically projecting basal forebrain neurons of various rodent species not previously examined. Double-label immunocytochemistry was performed using antibodies against calbindin-D 28k and choline acetyltransferase (ChAT) to detect the presence of the calcium binding protein within the cholinergic basal forebrain neurons of various species (i.e., humans, rats, mice, gerbils, guinea pigs). Antibodies against calbindin-D 28k, ChAT, and glutamic acid decarboxylase (GAD) were also used in combination with a cortically injected retrograde tracer (Fluoro-Gold) to determine whether calbindin-D 28k immunoreactive (IR) neurons within the basal forebrain projected to the frontoparietal cortex. The nucleus basalis of rats was examined for the presence of calbindin-D 28k IR within the GABAergic basal forebrain neurons. All species examined had cholinergic, GABAergic, and calbindinergic neurons within the basal forebrain; however, only the cholinergic neurons within the human nucleus basalis of Meynert were also immunoreactive for calbindin-D 28k. Although all rodent species had both cholinergic and GABAergic basal forebrain neurons that contained the Fluoro-Gold dye, none of the calbindin-D 28k IR neurons, detected using monoclonal and polyclonal antibodies, were found to contain the retrograde tracer. These results indicate that the cortically projecting cholinergic and GABAergic basal forebrain neurons within these rodent species do not contain calbindin-D 28k. Therefore, age- and disease-related loss of nucleus basalis projection neurons may not be mediated by alterations in calbindin-D 28k. Thus, rodents may not serve as an accurate model for either human aging or Alzheimer's disease as calbindin-D 28k is not found within the cortically projecting neurons of rodent species.