Conditionally immortalized cell lines, engineered to produce and release GABA, modulate the development of behavioral seizures.

摘要: Abstract Transplantation of genetically engineered cells can provide sustained focal delivery naturally occurring molecules, including neurotransmitters and growth factors. We have immortalized mouse cortical neurons glia to deliver GABA by driving GAD65 expression. Engineered cell lines showed mRNA expression, enzymatic activity, release. In vitro, basal flux was approximately 20% total cellular GABA. transplanted these GABA-producing bilaterally into either the anterior or posterior substantia nigra 43 rats. The rats were subsequently kindled through an electrode placed in entorhinal cortex. cells, but not β-galactosidase-producing affected kindling rates. number stimulations needed reach first stage-5 seizure achieve full differed significantly between transplantation sites when GAD65-producing transplanted. Our data show that make release at physiologically meaningful concentrations.