Partial kindling induces neurogenesis, activates astrocytes and alters synaptic morphology in the dentate gyrus of freely moving adult rats

A partial kindling procedure was used to investigate the correlation between focal seizure development and changes in dendritic spine morphology, ongoing neurogenesis and reactive astrogliosis in the adult rat dentate gyrus (DG). The processes of neurogenesis and astrogliosis were investigated using markers for doublecortin (DCX), 5-bromo-2-deoxyuridine (BrdU) and glial fibrillary acidic protein (GFAP). Our data demonstrate that mild focal seizures induce a complex series of cellular events in the DG one day after cessation of partial rapid kindling stimulation consisting (in comparison to control animals that were electrode implanted but unkindled), firstly, of an increase in the number of postmitotic BrdU labeled cells, and secondly, an increase in the number of DCX labeled cells, mainly in subgranular zone. Ultrastructural changes were examined using qualitative electron microscope analysis and 3-D reconstructions of both dendritic spines and postsynaptic densities. Typical features of kindling in comparison to control tissue included translocation of mitochondria to the base of the dendritic spine stalks; a migration of multivesicular bodies into mushroom dendritic spines, and most notably formation of “giant” spinules originating from the head of the spines of DG neurons. These morphological alterations arise at seizure stages 2–3 (focal seizures) in the absence of signs of the severe generalized seizures that are generally recognized as potentially harmful for neuronal cells. We suggest that an increase in ongoing neurogenesis, reactive astrogliosis and dendritic spine reorganization in the DG is the crucial step in the chain of events leading to the progressive development of seizure susceptibility in hippocampal circuits.