Newly born dentate granule neurons after pilocarpine-induced epilepsy have hilar basal dendrites with immature synapses

Abstract

Neurogenesis in the subgranular zone of the dentate gyrus persists throughout the lifespan of mammals, and the resulting newly born neurons are incorporated into existing hippocampal circuitry. Seizures increase the rate of neurogenesis in the adult rodent brain and result in granule cells in the dentate gyrus with basal dendrites. Using doublecortin (DCX) immunocytochemistry to label newly generated neurons the current study focuses on the electron microscopic features of DCX-labeled cell bodies and dendritic processes in the dentate gyrus of rats with pilocarpine-induced epilepsy. At the base of the granule cell layer clusters of cells that include up to six DCX-labeled cell bodies were observed. The cell bodies in these clusters lacked a one-to-one association with an astrocyte cell body and its processes, a relationship that is typical for newly born granule cells in control rats. Also, DCX-labeled basal dendrites in the hilus had immature synapses while those in control rats lacked synapses. These results indicate that increased neurogenesis after seizures alters the one-to-one relationship between astrocytes and DCX-labeled newly generated neurons at the base of the granule cell layer. The data also suggest that the synapses on DCX-labeled hilar basal dendrites contribute to the persistence of hilar basal dendrites on neurons born after pilocarpine-induced seizures.

Cdk6-Dependent Regulation of G1 Length Controls Adult Neurogenesis

“…In addition to transiently enhancing cell proliferation, seizures have been shown to increase the production of newborn neurons [51]. Importantly, these newborn neurons exhibit dramatic changes of neuronal polarity and migration, and integrate aberrantly into the pre-existing neuronal network [52][53][54], leading to longterm structural changes in the hippocampal circuitry that might contribute to chronic epilepsy [55,56]. To evaluate the consequences of Cdk6 deficiency on seizure-induced neurogenesis, we injected WT and Cdk6 À/À animals with BrdU 72 hours following seizure induction and sacrificed the animals 4 weeks later to quantify the number of BrdU þ surviving cells.…”

Pilocarpine-Induced Seizures Cause Selective Time-Dependent Changes to Adult-Generated Hippocampal Dentate Granule Cells

“…Traditional neuroanatomical methods, such as Golgi staining, provide detailed anatomical data but no direct information as to neuronal age (Spigelman et al, 1998;Buckmaster and Dudek, 1999;Yan et al, 2001). Markers of immature neurons, on the other hand, while providing information about the morphology of young cells, provide no information on mature cells (Shapiro et al, 2005;Overstreet-Wadiche et al, 2006b;Shapiro and Ribak, 2006). Viral labeling strategies, to our knowledge, would provide the best alternate means for comparing newborn cells labeled at different time points, although a recent report demonstrating fusion of viral-labeled microglia to mature neurons raises concerns (Ackman et al, 2006).…”

Altered hippocampal neurogenesis during the first 7 days after a fluid percussion traumatic brain injury

“…In the case of seizures, hilar ectopic granule cells have been demonstrated to contribute to a hyperexcitable recurrent hippocampal circuitry. 32,33 This circuit has also been demonstrated anatomically [15][16][17] and in previous studies using the same FPI model. It has been demonstrated that this model has anatomical alterations consistent with aberrant hippocampal circuitry.…”

“…A similar hypothesis has been previously postulated in models of epilepsy, in which hippocampal neurogenesis is also initially increased. [15][16][17] Such enhanced survival might also contribute to aberrant hippocampal circuit formation. [15][16][17] Considering that we have recently demonstrated a TBI-induced alteration to the radial glial-like processes in the dentate gyrus and that these cells provide a scaffold for the normal growth and integration of newborn granule cells, 11,21,22 it is possible that the alterations we have observed to hippocampal neurogenesis are related to hippocampal inflammation, including the activation of the radial glial-like astrocytes.…”

“…Neurogenic changes have also been linked to detrimental outcomes, including depression, fear responsiveness, increased seizure susceptibility, seizure generation, seizure facilitation, and the potential for development of epilepsy 15 ; development of epilepsy may possibly be due to improper migration and/or integration of new neurons into the existing hippocampal circuitry. 11,[15][16][17] In order to better understand the temporal effects of TBI on neurogenesis in the hippocampus, we used the fluid percussion injury (FPI) model and examined the quantity and location of newborn neurons in the hippocampus at 1 and 7 d after FPI or after a sham FPI. The hippocampi from these mice were processed for immunohistochemistry and labeled for immature neurons using antidoublecortin (DCX); the number of these cells was quantified, as were DCX-labeled cells in the hilus.…”