Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy

M. Paradisi, M. Fernández, G. Del Vecchio, G. Lizzo, G. Marucci, M. Giulioni, E. Pozzati, T. Antonelli, G. Lanzoni, G. P. Bagnara, L. Giardino and L. Calzà (2010) Neuropathology and Applied Neurobiology36, 535–550 Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe e...

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Published in:	Neuropathology and applied neurobiology 2010-10, Vol.36 (6), p.535-550
Main Authors:	Paradisi, M., Fernández, M., Del Vecchio, G., Lizzo, G., Marucci, G., Giulioni, M., Pozzati, E., Antonelli, T., Lanzoni, G., Bagnara, G. P., Giardino, L., Calzà, L.
Format:	Article
Language:	eng
Subjects:	Adolescent Adult adult human stem cells Biological and medical sciences Cell Proliferation dentate gyrus Dentate Gyrus - pathology Dentate Gyrus - physiopathology Epilepsy, Temporal Lobe - pathology Epilepsy, Temporal Lobe - physiopathology epileptogenesis Female Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy Humans Immunohistochemistry Male Medical sciences Nervous system (semeiology, syndromes) neural precursor cells neurogenesis Neurogenesis - physiology Neurology Neurons - cytology Reverse Transcriptase Polymerase Chain Reaction Sclerosis - pathology temporal lobe epilepsy
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Summary:	M. Paradisi, M. Fernández, G. Del Vecchio, G. Lizzo, G. Marucci, M. Giulioni, E. Pozzati, T. Antonelli, G. Lanzoni, G. P. Bagnara, L. Giardino and L. Calzà (2010) Neuropathology and Applied Neurobiology36, 535–550 Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy Aims: Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero‐mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. Methods: Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT‐PCR in neurospheres. Results: We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration. Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain‐derived neurotrophic factor, ciliary neurotrophic factor, glial‐derived neurotrophic factor, nerve growth factor). Conclusion: We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS.
ISSN:	0305-1846 1365-2990