Neurturin and persephin promote the survival of embryonic basal forebrain cholinergic neurons in vitro.
The GDNF family ligands (GFLs) are a group of neurotrophic factors that influence the development, survival, and maintenance of specific populations of neurons in the central and peripheral nervous systems. The cholinergic neurons of the basal forebrain provide cholinergic innervation to cortical structures and their integrity is vital to normal cognitive function. GDNF, the original member of the GFL family promotes the survival of developing basal forebrain cholinergic neurons in vitro. We have now found that neurturin (NRTN) and persephin (PSPN) also promote the survival of basal forebrain neurons including both cholinergic neurons and a population of non-cholinergic neurons with an efficacy comparable to NGF. We also demonstrate that developing and mature basal forebrain cholinergic neurons (BFCN) express GFL receptors. Ret, the signaling component of the GFL-receptor complex, is expressed in most adult rat BFCN. In addition, Ret and the GFL co-receptors GFRalpha1 and GFRalpha2 are expressed in developing cholinergic neurons in cultures of embryonic basal forebrain. Our results suggest that the GFLs may be effective as neuroprotective agents for BFCNs in vivo.
Golden
Judith P
JP
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA. jgolden@msnotes.wustl.edu
Milbrandt
Jeffrey
J
Johnson
Eugene M
EM
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers; D002352:Carrier Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051101:Neurturin; D010275:Parasympathetic Nervous System / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D015415:Biomarkers; D002352:Carrier Proteins; C495041:Gdnf protein, rat; C494992:Gfra2 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495057:Nrtn protein, rat; D011518:Proto-Oncogene Proteins; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C110758:persephin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C495001:Ret protein, rat