Premium
GDNF is a Trophic Factor for Adult Rat Corticospinal Neurons and Promotes their Long‐term Survival after Axotomy In vivo
Author(s) -
Giehl Klaus M.,
Schacht Claudia M.,
Yan Qiao,
Mestres Pedro
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01665.x
Subject(s) - axotomy , glial cell line derived neurotrophic factor , neuroscience , in vivo , neurotrophic factors , trophic level , biology , central nervous system , receptor , ecology , biochemistry , microbiology and biotechnology
Glial cell line‐derived neurotrophic factor (GDNF) is a trophic factor for several neuronal populations involved in motor control. The present study evaluates the trophic actions of GDNF on corticospinal neurons, an important central nervous system motor projection into the spinal cord. Death of spinal motoneurons and corticospinal neurons is observed in the neurodegenerative disease amyotrophic lateral sclerosis. Axotomy of adult rat corticospinal neurons at internal capsule levels induces half of them to die, and the surviving population displays severe atrophy. To examine the trophic effects of GDNF on corticospinal neurons, Fast Blue‐labelled corticospinal neurons were stereotaxically axotomized at internal capsule levels and GDNF was infused intracortically to lesioned corticospinal neurons at total doses of 2, 4, 10, 20, 40, 100 and 300 μg for 7 days. GDNF prevented axotomy‐induced death of corticospinal neurons at doses between 2 and 40 μg and abolished or attenuated their atrophy at all doses examined. In addition, treatment with 8 μg GDNF for the first 2 weeks after axotomy resulted in the long‐term survival of corticospinal neurons for 42 days. With regard to the development of treatment strategies for upper motoneuron degeneration in amyotrophic lateral sclerosis, application of GDNF via the cerebrospinal fluid may be more relevant than intracortical delivery as its diffusion within the brain parenchyma is limited. lntraventricular as well as intracisternal infusion of GDNF (300 μg over 7 days) completely prevented corticospinal neuron death. These results show that GDNF promotes the long‐term survival of corticospinal neurons and has a positive effect on their size in vivo Furthermore, the survival‐promoting effect of GDNF on corticospinal neurons after delivery via cerebrospinal fluid has important clinical implications for potential treatment of the upper motoneuron degeneration seen in amyotrophic lateral sclerosis.