Premium
[P2.19]: Effect of valproic acid on hippocampal dependent cognition and proliferation
Author(s) -
Umka J.,
Thrope A.,
Mustafa S.,
Wigmore P.
Publication year - 2008
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2008.09.144
Subject(s) - library science , citation , psychology , sociology , computer science
Embryonic stem cell (ES)-based therapy is a potential approach for treatingneurological disorders, including intractableepilepsy. ES cells can be used to generate functionally identified neurons or neural precursors for transplantation in large quantities, however little is known about how to direct the fates of ES cells toward specific neuronal or glial lineages needed for treating specific neurological disorders. Previous resultswith YC5 ES line established that transplanted ESNPs survive for long periods and incorporate into the hippocampus. Themajoritymigrate throughout the dentate gyrus and integrate into the subgranular zone. Increasingly, methods are being developed for directing ES cells toward specific neuronal fates usingmolecular genetic approaches or by addition of extrinsic growth factors to the ES growth media. We are testing whether replacing damaged GABAergic interneurons with ESderived neural precursors (ESNPs) is an effective treatment for controlling seizures in a mouse model of temporal lobe epilepsy (TLE). GABAmodulates levels of excitation in the dentate gyrus, and loss of inhibitory tone leads to spontaneous seizures in both human patients with TLE and animalmodels of TLE. To direct ESNPs toward GABAergic fates, we use ES cells with constitutive RFP and GFP driven by the sox1-promoter. ES cells are treated with conditioned media from primary cultures from the ganglionic eminences, to direct their fates towardGABAergic phenotypes.We then enrich the Sox-1 GFP expressing neural precursors by FACS prior to transplantation. ESNPs ( 50,000 cells), including GABAergic neural progenitors, were stereotaxically grafted into the dentate gyrus in mice with TLE, caused by an initial episode of pilocarpine-induced status epilepticus. We are analyzing the fates of transplanted ESNPs by immunohistochemistry and electrophysiology to determine whether they differentiate into granule neurons or GABAergic neurons, or retain progenitor fates. Research support: McKnight Brain Disorders Award and Connecticut Stem Cell Initiative.