Astrocytes retrovirally transduced with BDNF elicit behavioral improvement in a rat model of Parkinson's disease

Brain Research
Y YoshimotoM C Bohn

Abstract

Neurotrophic factors that improve the survival of specific neuronal types during development and after exposure to various neuronal insults hold potential for treatment of neurodegenerative diseases. In particular, brain-derived neurotrophic factor (BDNF) has been shown to exert trophic and protective effects on dopaminergic neurons, the cell type known to degenerate in Parkinson's disease. To determine whether increased levels of biologically produced BDNF affect the function or regeneration of damaged dopaminergic neurons, the effects of grafting astrocytes transduced with the human BDNF gene into the striatum of the partially lesioned hemiparkinsonian rat were examined. Replication deficient retroviruses carrying either human prepro-BDNF or human alkaline phosphatase (AP) cDNA were used to transduce primary type 1 astrocytes purified from neonatal rat cortex. In vitro, BDNF mRNA was expressed by BDNF transduced astrocytes (BDNF astrocytes), but not control AP transduced astrocytes (AP astrocytes), as determined by reverse transcription polymerase chain reaction (RT-PCR). The modified astrocytes were injected into the right striatum 15 days after partial lesioning of the right substantia nigra with 6-hydroxydopamine. Transpla...Continue Reading

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