Abstract
Previous studies showed that neurogenesis occurs in the dentate gyrus of the adult rodent. Recent evidence suggests that the resulting newly born neurons integrate into pre-existing hippocampal circuitry. Newly born neurons in the developing and adult dentate gyrus exhibit a transient basal dendrite. In adult pilocarpine-induced epileptic rats, basal dendrites persist and are ectopically located in the hilus where they receive synaptic input from mossy fiber axons. We hypothesize that these hilar basal dendrites are derived from newly born neurons that are born after the pilocarpine-induced seizures. To test this hypothesis, the length of basal dendrites from epileptic rats was compared with that from control rats using doublecortin immunocytochemistry, which labels newly born neurons and their processes for up to 3 weeks after their genesis. The data on hilar basal dendrites in pilocarpine animals indicate that those from newly born neurons are significantly longer than those found in the control rats. We also demonstrate that 20% of newly born neurons in the epileptic rat have a basal dendrite that enters the hilus at an angle greater than 30° from its cell body as compared with <2% in the control rats. Lastly, we provide evidence that the hilar basal dendrites in the epileptic rats are adjacent to glial fibrillary acidic protein-labeled astrocytic processes in the hilus and suggest that an ectopic glial scaffold in the hilus is involved with the formation of hilar basal dendrites. In conclusion, the data show that newly born neurons from epileptic rats have longer hilar basal dendrites and their formation might relate to gliosis which occurs as a result of hilar neuronal cell loss after status epilepticus.
Highlights
Several studies used nuclear markers such as bromodeoxyuridine (BrdU) and [3H]thymidine to label the NNs, while others have incorporated more structurally revealing immunohistochemical markers such as TUC-4, -III-tubulin, Prox-1, CRMP-4, and doublecortin (DCX) to analyze these newly generated granule cells
NNs in the dentate gyrus of controls have basal dendrites adjacent to glial cells Most of the DCX-labeled granule cells in the subgranular zone (SGZ) were located within 30 m of the granule cell layer (GL) (Fig. 1)
Many dendrites remained in the SGZ, whereas others curved into the GL as described for recurrent basal dendrites (Figs. 1 and 3)
Summary
Several studies used nuclear markers such as bromodeoxyuridine (BrdU) and [3H]thymidine to label the NNs, while others have incorporated more structurally revealing immunohistochemical markers such as TUC-4, -III-tubulin, Prox-1, CRMP-4, and doublecortin (DCX) to analyze these newly generated granule cells. In addition to an apical dendrite, 31%–55% of newly born granule cells exhibit a basal dendrite (Rao and Shetty, 2004; Ribak et al, 2004), which appears to be transient for granule cells during neonatal development (Seress and Pokorny, 1981; Jones et al, 2003). It is possible that the appearance of granule cells with HBDs in epileptic rats is related to the overall increase in neurogenesis following pilocarpine-induced seizures (Parent et al, 1997) Unlike normal development, these latter basal dendrites are a persistent feature of granule cells in epileptic rats and represent a seizure-induced neuro-. One of the goals of the present study is to determine whether HBDs arise from NNs that are born after the induction of status epilepticus by pilocarpine-treatment
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