Impaired migration in the rostral migratory stream but spared olfactory function after the elimination of programmed cell death in Bax knock-out mice.
Rats and mice exhibit neurogenesis of olfactory bulb (OB) interneurons throughout adulthood. To homeostatically maintain stable neuron numbers, it is necessary to continuously remove a subset of OB neurons by programmed cell death (PCD). Here we demonstrate that Bax is critical for the elimination of OB neurons by showing that Bax-KO mice exhibit greatly reduced PCD in the OB. Despite the reduction of PCD, however, proliferation of progenitors and the size of the OB were virtually unaffected in Bax-knock-out (KO) mice. However, reducing PCD by Bax deletion affected the migration of a subset of adult-produced neurons by the disruption of glial tube formation as well as by premature detachment of neuroblasts from the migratory chain. Rescued cells aberrantly remained in the subventricular zone (SVZ)-rostral migratory stream (RMS), in which they differentiated into calretinin+ or GABA-expressing interneurons. Because of the migratory deficit, OB cell homeostasis involving new cell entry and PCD (neuronal turnover) was virtually absent in adult Bax-KO mice. Despite this, Bax-KO mice exhibited normal olfactory behaviors such as odor discrimination and olfactory memory which are thought to be influenced by adult neurogenesis. These results demonstrate that PCD is involved in the regulation of RMS migration and differentiation after OB neurogenesis, but that animals maintain normal olfactory function in the absence of PCD.
Kim
Woon Ryoung
WR
Department of Anatomy, College of Medicine, Korea University, Sungbuk-Gu, Seoul 136-705, Korea.
Kim
Younghwa
Y
Eun
Bokkee
B
Park
Ok-hee
OH
Kim
Hyun
H
Kim
Kyungjin
K
Park
Chang-Hwan
CH
Vinsant
Sharon
S
Oppenheim
Ronald W
RW
Sun
Woong
W
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001973:Bromodeoxyuridine / Q000378:metabolism; D064032:Calbindin 2; D016923:Cell Death / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D048429:Cell Size; D000089622:Doublecortin Domain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000172:deficiency*
C494827:Bax protein, mouse; C576511:Calb2 protein, mouse; C576512:Calb2 protein, rat; D064032:Calbindin 2; D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018809:Proliferating Cell Nuclear Antigen; D064030:S100 Calcium Binding Protein G; D051028:bcl-2-Associated X Protein; D001973:Bromodeoxyuridine