Concentration- and cell type-specific effects of calbindin D28k on vulnerability of hippocampal neurons to seizure-induced injury

The calcium-binding protein calbindin D28k (CB) is expressed in limited sub populations of neurons in the brain. In the hippocampus, CB is expressed in all dentate granule cells and a subpopulation of CA1 pyramidal neurons, bu t is absent from CA3 neurons. This pattern of CB expression is inversely co rrelated with neuronal vulnerability to seizure-induced damage suggesting t he possibility that expression of CB confers resistance to excitotoxicity. While data from cell culture studies support an excitoprotective role for c albindin, it is not known whether CB is a key determinant of neuronal vulne rability in vivo. We therefore examined the pattern of damage to hippocampa l neurons following intrahippocampal injection of the seizure-inducing exci totoxin kainate in CB homozygous (CB -/-) and CB heterozygous (CB +/-) knoc kout mice in comparison with wild-type mice (CB +/+). Whereas the extent of damage to CA1 neurons was similar in CB -/- and CB +/+ mice, damage to CA1 neurons was significantly reduced in CB +/- mice. Dentate granule neurons were not damaged following kainate-induced seizures in CB +/+, CB +/- or CB -/- mice. These findings suggest that CB can modify vulnerability of hippo campal CA1 neurons to seizure-induced injury, and that either CB is not a c ritical determinant of resistance of dentate granule neurons, or compensato ry changes occur and lack of CB is not the only difference between CB -/- a nd CB +/+ mice. (C) 2000 Elsevier Science B.V. All rights reserved.