Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures

• Published in: Brain research 2007-02, Vol.1133 (1), p.10-19
• Main Authors: Bjerkén, Sara af, Boger, Heather A, Nelson, Matthew, Hoffer, Barry J, Granholm, Ann-Charlotte, Strömberg, Ingrid
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Astrocytes - metabolism; Astroglia; Axons - drug effects; Axons - metabolism; Axons - ultrastructure; Biological and medical sciences; Cell Communication - drug effects; Cell Communication - genetics; Cell Movement - drug effects; Cell Movement - genetics; Cell physiology; Cell Survival - drug effects; Cell Survival - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine; Dopamine - metabolism; Female; Fundamental and applied biological sciences. Psychology; GDNF; Glial Cell Line-Derived Neurotrophic Factor - genetics; Glial Cell Line-Derived Neurotrophic Factor - pharmacology; Growth Cones - metabolism; Immunohistochemistry; Knockout; Male; Medical sciences; Mesencephalon - cytology; Mesencephalon - embryology; Mesencephalon - metabolism; Mice; Mice, Knockout; Molecular and cellular biology; Neural plasticity; Neurology; Organ Culture Techniques; Organic mental disorders. Neuropsychology; Organotypic culture; Parkinson's disease; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Responses to growth factors, tumor promotors, other factors; Substantia Nigra - cytology; Substantia Nigra - embryology; Substantia Nigra - metabolism; Tyrosine 3-Monooxygenase - metabolism; Ventral mesencephalon
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.11.052

Abstract Glial cell line-derived neurotrophic factor (GDNF) is potent for survival and promotion of nerve fibers from midbrain dopamine neurons. It is also known to exert different effects on specific subpopulations of dopamine neurons. In organotypic tissue cultures, dopamine neurons form two diverse nerve fiber growth patterns, targeting the striatum differently. The aim of this study was to investigate the effect of GDNF on the formation of dopamine nerve fibers. Organotypic tissue cultures of ventral mesencephalon of gdnf gene-deleted mice were studied. The results revealed that dopamine neurons survive in the absence of GDNF. Tyrosine hydroxylase immunoreactivity demonstrated, in gdnf knockout and wildtype cultures, nerve fiber formation with two separate morphologies occurring either in the absence or the presence of astrocytes. The outgrowth that occurred in the absence of astrocytes was unaffected by gdnf deletion, whereas nerve fibers guided by the presence of astrocytes were affected in that they reached significantly shorter distances from the gdnf gene-deleted tissue slice, compared to those measured in wildtype cultures. Treatment with GDNF reversed this effect and increased nerve fiber density independent of genotype. Furthermore, migration of astrocytes reached significantly shorter distances from the tissue slice in GDNF knockout compared to wildtype cultures. Exogenous GDNF increased astrocytic migration in gdnf gene-deleted tissue cultures, comparable to lengths observed in wildtype tissue cultures. In conclusion, cultured midbrain dopamine neurons survive in the absence of GDNF, and the addition of GDNF improved dopamine nerve fiber formation — possibly as an indirect effect of astrocytic stimulation.