Novel role for aspartoacylase in regulation of BDNF and timing of postnatal oligodendrogenesis.
Neuronal growth factors are thought to exert a significant degree of control over postnatal oligodendrogenesis, but mechanisms by which these factors coordinateoligodendrocyte development with the maturation of neural networks are poorly characterized. We present here a developmental analysis of aspartoacylase (Aspa)-null tremor rats and show a potential role for this hydrolytic enzyme in the regulation of a postnatal neurotrophic stimulus that impacts on early stages of oligodendrocyte differentiation. Abnormally high levels of brain-derived neurotrophic factor (BDNF) expression in the Aspa-null Tremor brain are associated with dysregulated oligodendrogenesis at a stage in development normally characterized by high levels of Aspa expression. BDNF promotes the survival of proliferating cells during the early stages of oligodendrocyte maturation in vitro, but seems to compromise the ability of these cells to populate the cortex in vivo. Aspartoacylase activity in oligodendrocytes is shown to provide for the negative regulation of BDNF in neurons, thereby determining the availability of a developmental stimulus via a mechanism that links oligodendroglial differentiation with neuronal maturation.
Francis
Jeremy S
JS
Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey,Camden, NJ, USA.
Olariu
Ana
A
McPhee
Scott W
SW
Leone
Paola
P
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000367:Age Factors; D000581:Amidohydrolases / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005455:Fluorescent Antibody Technique / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D017403:In Situ Hybridization / Q000379:methods; D004676:Myelin Basic Protein / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014202:Tremor / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000581:Amidohydrolases; C019751:aspartoacylase; D001973:Bromodeoxyuridine