The Neurogenic Niche of Human Hippocampus in Mesial Temporal Lobe Epilepsy

Martín-Suárez, S. 1, 2 , Valcárcel-Martín, R. 1, 2 , Marinas, A. 3 , Zaldumbide, L. 3 , Sierra, A. 1, 2, 4 & Encinas, J. M. 1, 2, 4

1 Achucarro Basque Center for Neuroscience
2 University of the Basque Country (UPV/EHU)
3 Hospital Universitario de Cruces
4 Ikerbasque, the Basque Science Foundation

Mesial Temporal Lobe Epilepsy (MTLE), the most common form of drug-resistant epilepsy, affects the hippocampus and related limbic structures. MTLE is characterized by recurrent focal seizures and the development of hippocampal sclerosis. Typical landmarks of hippocampal sclerosis are neuronal death and dispersion; and gliosis with massive presence of reactive astrocytes. The hippocampus is one of the two areas where neurogenesis, the formation of new neurons, takes place in the adult brain. Hippocampal neurogenesis is important for spatial memory and learning; pattern separation; and the responses to fear, anxiety and stress and pattern association memory. The effect of seizures on hippocampal neurogenesis has been studied but opposite results has been reported.

Working with mice and an experimental model of MTLE we have determined that neurogenesis is impaired in the long term. Impaired neurogenesis might have two detrimental effects: a loss of the functions associated with neurogenesis, and a loss of the restorative potential of neural stem cells. We are currently analyzing human hippocampi from MTLE patients and our preliminary results show, in agreement with our findings in mice, that putative neural stem cells, cell proliferation and newborn neurons are absent in the epileptic human hippocampus. We hypothesize that impairment of neurogenesis might contribute to the cognitive deficits and psychiatric comorbidities associated with MTLE in humans.