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Preparation of Acute Human Hippocampal Slices for Electrophysiological Recordings
Published on: May 7, 2020
Doublecortin expression in the normal and epileptic adult human brain
Y W J Liu1, M A Curtis, H M Gibbons
1Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Abstract:
Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.
Insights
New neurons may be generated in the adult human temporal cortex in mesial temporal lobe epilepsy (MTLE). This study found increased doublecortin (Dcx)-positive cells in epilepsy patients, suggesting a role in neurological disease.
Area of Science:
- Neuroscience
- Epilepsy Research
- Cell Biology
Background:
- Mesial temporal lobe epilepsy (MTLE) is characterized by recurrent seizures and hippocampal damage.
- While animal models show increased neurogenesis in MTLE, this has not been confirmed in adult humans.
- Understanding neurogenesis in human epilepsy is crucial for pathophysiology insights.
Purpose of the Study:
- To investigate the presence and characteristics of neuroblast markers in the adult human temporal cortex in MTLE.
- To determine if epilepsy influences the generation of new neurons in the temporal cortex.
- To explore the potential functional role of these cells in epilepsy.
Main Methods:
- Immunohistochemistry was used to identify doublecortin (Dcx)-positive cells in human temporal cortex and hippocampus samples from normal and MTLE individuals.
- Co-expression analysis was performed using markers for proliferation (proliferating cell nuclear antigen) and neuronal differentiation (TuJ1, NeuN).
Main Results:
- Doublecortin (Dcx)-positive cells, indicative of migrating neuroblasts, were found in both normal and MTLE adult human brains.
- Significantly higher numbers of Dcx-positive cells were observed in the temporal cortex of MTLE patients compared to controls.
- A substantial portion of Dcx-positive cells in the epileptic temporal cortex co-expressed markers for proliferation and early neuronal development, with some also expressing mature neuronal markers.
Conclusions:
- This study identifies a novel population of Dcx-positive cells in the adult human temporal cortex.
- Epilepsy appears to upregulate these Dcx-positive cells, suggesting increased neurogenesis in the temporal cortex.
- These findings raise the possibility of a functional role for newly generated neurons in the pathophysiology of human temporal lobe epilepsy.
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