GDNF prevents degeneration and promotes the phenotype of brain noradrenergic neurons in vivo.
The locus coeruleus (LC), the main noradrenergic center in the brain, participates in many neural functions, as diverse as memory and motor output, and is severely affected in several neurodegenerative disorders of the CNS. GDNF, a neurotrophic factor initially identified as dopaminotrophic, was found to be expressed in several targets of central noradrenergic neurons in the adult rat brain. Grafting of genetically engineered fibroblasts expressing high levels of GDNF prevented > 80% of the 6-hydroxydopamine-induced degeneration of noradrenergic neurons in the LC in vivo. Moreover, GDNF induced a fasciculated sprouting and increased by 2.5-fold both tyrosine hydroxylase levels and the soma size of lesioned LC neurons. These findings reveal a novel and potent neurotrophic activity of GDNF that may have therapeutic applications in neurodegenerative disorders affecting central noradrenergic neurons, such as Alzheimer's, Parkinson's, and Huntington's diseases.
Arenas
E
E
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Trupp
M
M
Akerud
P
P
Ibáñez
C F
CF
D000818:Animals; D002460:Cell Line; D005818:Genetic Engineering; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008125:Locus Coeruleus / Q000166:cytology / Q000502:physiology*; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016627:Oxidopamine; D009638:Norepinephrine