Repeated PTZ Treatment at 25-Day Intervals Leads to a Highly Efficient Accumulation of Doublecortin in the Dorsal Hippocampus of Rats

Abstract

BackgroundNeurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility.Methodology/Principal FindingsBy EEG, RT-PCR, western blotting and immunohistochemistry, we show that repeated convulsive seizures with a periodicity of 25±1 days led to an enrichment of newly generated neurons, that were BrdU-positive in the dentate gyrus at day 25±1 post-seizure. At the same time, there was a massive increase in the number of neurons expressing the migratory marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus. Some of these migrating neurons were also positive for NeuN, a marker for adult neurons.Conclusion/SignificanceOur results suggest that the increased susceptibility to seizure at day 25±1 post-treatment is coincident with a critical time required for newborn neurons to differentiate and integrate into the existing hippocampal network, and outlines the importance of the dorsal hippocampus for seizure-related neurogenesis. This model can be used as an in vivo correlate of neurogenesis to study basic questions related to neurogenesis and to the neurogenic mechanisms that contribute to the development of epilepsy.

RETRACTED: Suppression of epileptogenesis-associated changes in response to seizures in FGF22-deficient mice

“…At the basal level (PBS-injected mice), we found less DCX-positive cells in the DG in FGF22KO mice than in WT mice (Figure 3B), suggesting that FGF22 is involved in neuronal differentiation. The number of DCX-positive cells was increased in WT mice with kindled seizures, which is consistent with previous reports (Parent et al, 2006; Jessberger et al, 2007; Yin et al, 2007; Buga et al, 2012). It was similarly increased in WT mice with mild seizures.…”

Roles of Matrix Metalloproteinases and Their Targets in Epileptogenesis and Seizures

“…A dramatic increase in the production of new cells and neurons was observed in the subgranular zone and granule cell layer of the dentate gyrus following pilocarpine-induced status epilepticus41) or kindling 42). Repeated administration of PTZ,43) kainic acid,44,45) or pilocarpine46) also increased neurogenesis in the hippocampus. In fact, kainic acid-induced seizures increased the proliferation, migration, and survival of neural progenitors in the dentate gyrus, and severe seizures have been linked to aberrant migration of newborn neurons into the dentate hilus 45).…”

Pentylenetetrazol Kindling Epilepsy Model

“…[32] Animals are placed in the stereotaxic frame. [33] By the guidance of stereotaxic atlas, electrodes are placed into the intended coordinates. [29] They are fixed with screw, covered with cold acrylic and sculp is sutured.…”

“…[32] Following the surgery, 1 week is passed for healing of local effects of surgery and anesthesia before monitoring procedure. [33] Action mechanism of PTZ PTZ is a selective antagonist of receptor of GABAA chloride ionophore complex. It has convulsive activity when used alone or in repetitive doses.…”