Mice lacking NT-3, and its receptor TrkC, exhibit profound deficiencies in CNS glial cells.
Neurotrophin-3 (NT-3) and its receptor TrkC are known to be important for neuronal survival. More recently, NT-3 has been implicated as playing a role in oligodendrocyte (OL) proliferation and survival in vitro. Examination of NT-3 and TrkC knockout mice revealed a reduction in NT-3-dependent neurons. To date, no study has examined alterations in glial cell populations in these knockout mice. In this report, we demonstrate a decline in OL progenitor cell numbers within the CNS of NT-3 and TrkC knockout mice. We also observed that immature and mature OL-specific markers were attenuated in the NT-3 and TrkC knockout animals. Deficiencies in other CNS glial cells, including astrocytes and ameboid microglia, were also observed. The subventricular zone (SVZ), a highly proliferative region for progenitor glial cells, was reduced in size. Furthermore, a nuclear-specific stain revealed a decline in the numbers of pyknotic nuclei in and around the SVZ of the knockout mice. These data will support an in vivo NT-3-dependent mechanism for the normal development of CNS glial cells.
Kahn
M A
MA
Department of Neurobiology, UCLA School of Medicine, USA.
Kumar
S
S
Liebl
D
D
Chang
R
R
Parada
L F
LF
De Vellis
J
J
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D015415:Biomarkers; D002452:Cell Count; D016922:Cellular Senescence / Q000502:physiology; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology; D002552:Cerebral Ventricles / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D020933:Neurotrophin 3; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics; D013116:Spinal Cord / Q000473:pathology; D013234:Stem Cells / Q000473:pathology
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC