New neurons in the vestibular nuclei complex after unilateral vestibular neurectomy in the adult cat

Abstract

Recent findings revealed a reactive neurogenesis after lesions and in several models of disease. After unilateral vestibular neurectomy (UVN), we previously reported gamma-aminobutyric acid (GABA)ergic neurons are upregulated in the vestibular nuclei (VN) in the adult cat. Here, we ask whether this upregulation of GABAergic neurons resulted from a reactive neurogenesis. To determine the time course of cell proliferation in response to UVN, 5-bromo-2'-deoxyuridine (BrdU) was injected 3 h, 1, 3, 7, 15 and 30 days after UVN. We investigated the survival and differentiation in UVN cats injected with BrdU at 3 days and perfused 30 days after UVN. Results show a high number of BrdU-immunoreactive nuclei in the deafferented VN with a peak at 3 days after UVN and a decrease at 30 days. Most of the newly generated cells survived up to 1 month after UVN and gave rise to a variety of cell types. Confocal analysis revealed three cell lineages: microglial cells (OX 42/BrdU-immunoreactive cells); astrocytes [glial fibrillary acidic protein (GFAP)/BrdU-immunoreactive cells]; and neurons (NeuN/BrdU-immunoreactive cells). That UVN induced new neurons was confirmed by an additional marker (nestin) expressed by neural precursor cells. We show that most of the newly generated neurons have a GABAergic phenotype [glutamate decarboxylase (GAD)-67/BrdU-immunoreactive cells]. Morphological analysis showed two subtypes of GABAergic neurons: medium and small (30 vs. 10 microm, respectively). This is the first report of reactive neurogenesis in the deafferented VN in the adult mammalian CNS.