Expression of BCL-2 via adeno-associated virus vectors rescues thalamic neurons after visual cortex lesion in the adult rat.
Lesions of the mammalian visual cortex cause the retrograde degeneration of the thalamic neurons projecting to the damaged cortex. The proto-oncogene bcl-2 is known to inhibit neuronal apoptosis induced by a variety of noxious stimuli and preserve the functional integrity of the injured cells. Here we have tested whether the overexpression of bcl-2 via adeno-associated virus (AAV) vectors is able to protect the neurons in the lateral geniculate nucleus after visual cortex ablation in adult rats. Recombinant AAV vectors encoding Bcl-2 (AAV-Bcl-2) or green fluorescent protein (AAV-GFP) as a control were stereotaxically injected into the geniculate. Three weeks after vector injection, the ipsilateral visual cortex was removed by aspiration, and cell survival was assessed 2 weeks later. We found that 20% of the geniculate neurons were transduced by the Bcl-2 vector. These cells were completely protected from death following cortical ablation. Delivery of AAV-GFP transduced an identical number of geniculate neurons but had no effect on cell survival after lesion. The total number of surviving geniculate neurons was found to be significantly higher in animals injected with AAV-Bcl-2 than in rats injected with AAV-GFP or in control lesioned rats. These data indicate that Bcl-2 gene therapy with AAV vectors represents an effective treatment to promote neuronal survival after central nervous system insults.
Caleo
Matteo
M
Scuola Normale Superiore, P.zza dei Cavalieri 7, 56126 Pisa, Italy. caleo@in.pi.cnr.it
Cenni
Maria Cristina
MC
Costa
Mario
M
Menna
Elisabetta
E
Zentilin
Lorena
L
Giadrossi
Sara
S
Giacca
Mauro
M
Maffei
Lamberto
L
D000818:Animals; D001284:Atrophy / Q000473:pathology; D019771:Axotomy; D002452:Cell Count; D048429:Cell Size / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D000229:Dependovirus / Q000235:genetics*; D005456:Fluorescent Dyes; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D005829:Geniculate Bodies / Q000166:cytology / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012183:Retrograde Degeneration / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D013266:Stilbamidines; D014793:Visual Cortex / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D014795:Visual Pathways / Q000166:cytology / Q000293:injuries / Q000378:metabolism
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D013266:Stilbamidines