TY - JOUR T1 - Complete and Long-Term Rescue of Lesioned Adult Motoneurons by Lentiviral-Mediated Expression of Glial Cell Line-Derived Neurotrophic Factor in the Facial Nucleus JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5587 LP - 5593 DO - 10.1523/JNEUROSCI.20-15-05587.2000 VL - 20 IS - 15 AU - Andreas F. Hottinger AU - Mimoun Azzouz AU - Nicole Déglon AU - Patrick Aebischer AU - Anne D. Zurn Y1 - 2000/08/01 UR - http://www.jneurosci.org/content/20/15/5587.abstract N2 - To date, delivery of neurotrophic factors has only allowed to transiently protect axotomized facial motoneurons against cell death. In the present report, long-term protection of these neurons was evaluated by continuously expressing the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) within the facial nucleus using a lentiviral vector system. The viral vector was injected unilaterally into the facial nucleus of 4-month-old Balb/C mice. In contrast to axotomy in other adult rodents, facial nerve lesion in these animals leads to a progressive and sustained loss and/or atrophy of >50% of the motoneurons. This model thus represents an attractive model to evaluate potential protective effects of neurotrophic factors for adult-onset motoneuron diseases, such as amyotrophic lateral sclerosis. One month after unilateral lentiviral vector injection, the facial nerve was sectioned, and the animals were killed 3 months later. Viral delivery of the GDNF gene led to long-term expression and extensive diffusion of GDNF within the brainstem. In addition, axotomized motoneurons were completely protected against cell death, because 95% of the motoneurons were present as demonstrated by both Nissl staining and choline acetyltransferase immunoreactivity. Furthermore, GDNF prevented lesion-induced neuronal atrophy and maintained proximal motoneuron axons, despite the absence of target cell reinnervation. This is the first evidence that viral-mediated delivery of GDNF close to the motoneuron cell bodies of the facial nucleus of adult mice can lead to complete and long-term protection against lesion-induced cell death. ER -