Increased proliferation of precursor cells in the adult rat brain after targeted lesioning

There have been a number of reports on the proliferation of a subset of precursor cells in the subventricular zone of the lateral ventricles in the adult mammalian brain. Here we report on studies that sought to ascertain whether these cells could respond to a targeted lesion of the adult brain by increasing their proliferative rate. We have lesioned the fimbria fornix, a major pathway of septal cholinergic fibers. Previous reports demonstrated that such a lesion results in the loss of neurons in both the basal forebrain and in the CA1 field of hippocampus, without direct injury to either tissue. Ten days after making such a lesion in adult rats, the animals were given serial injections of [3H]thymidine and sacrificed after a final injection. The brains were processed for both immunocytochemistry and autoradiography. Our data demonstrate a two-fold increase over the basal proliferative rate in animals that had received such a lesion. We used a panel of antibodies to ascertain the identity of the proliferating cells. The only clearly identifiable cells that were [3H]thymidine-positive were astrocytes, based on GFAP staining. The remainder of the cells were of a null phenotype.