Cyclosporine A reduces dendritic outgrowth of neuroblasts in the subgranular zone of the dentate gyrus in C57BL/6 mice.
In the present study, we observed the effects of cyclosporine A (CsA), an efficient immunosuppressant, on cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus (SZDG) in normal C57BL/6 mice using Ki67 and doublecortin (DCX) immunohistochemical staining, respectively. At 8 weeks of age, vehicle (physiological saline) or CsA was daily administered (40 mg/kg, i.p.) for 1 week. Animals were sacrificed at 2 weeks after last administration. CsA treatment did not show any influences in neurons, astrocytes and microglia based on immunohistochemistry for its markers, respectively. However, in the CsA-treated group, Fluoro-Jade B, a marker for neurodegeneration, positive cells were found in the SZDG, not in the vehicle-treated group. In the vehicle-treated group, Ki67 immunoreactive (+) nuclei were clustered in the SZDG, whereas in the CsA-treated group Ki67(+) nuclei were scattered in the SZDG, showing no difference in cell numbers. Numbers of DCX(+) neuroblasts with well-developed processes (tertiary dendrites) were much lower in the CsA-treated group than those in the vehicle-treated group; however, numbers of DCX(+) neuroblasts with secondary dendrites were similar in both the groups. These results suggest that CsA significantly reduces dendritic outgrowth and complexity from neuroblasts in the SZDG without any affecting in neurons, astrocytes and microglia in normal mice.
Department of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea.
In Koo
IK
Hwang
Sun Shin
SS
Yi
Jae Hoon
JH
Shin
Ki-Yeon
KY
Yoo
Jung Hoon
JH
Choi
Choong Hyun
CH
Lee
Je Kyung
JK
Seong
Yeo Sung
YS
Yoon
Jeong Ho
JH
Park
Moo-Ho
MH
Won
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects*; D004268:DNA-Binding Proteins; D003712:Dendrites / Q000187:drug effects*; D018891:Dentate Gyrus / Q000473:pathology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009930:Organic Chemicals
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009479:Neuropeptides; D009687:Nuclear Proteins; D009930:Organic Chemicals; C435731:fluoro jade; D016572:Cyclosporine