Decreased brain zinc availability reduces hippocampal neurogenesis in mice and rats.
In the adult brain, neurogenesis occurs in the subgranular zone of the dentate gyrus (DG), where high levels of vesicular zinc are localized in the presynaptic terminals. To determine whether zinc has a role in modulating hippocampal neurogenesis under normal or pathologic conditions, we manipulated the level of vesicular zinc experimentally. To reduce hippocampal vesicular zinc, rats were either fed a zinc-deficient diet or treated with a zinc chelator, clioquinol (CQ). The number of progenitor cells and immature neurons was decreased significantly in the DG after 6 weeks of dietary zinc deprivation. Conversely, the number of progenitor cells and immature neurons was restored after a 2-week reversal to a normal zinc-containing diet. Similarly, a 1-week treatment with the zinc chelator, CQ, reduced the number of progenitor cells. The results of our previous study showed that hypoglycemia increased hippocampal neurogenesis. This study shows that zinc chelation reduced hypoglycemia-induced progenitor cell proliferation and neurogenesis. Finally, the role of vesicular zinc on neurogenesis was further assessed in zinc transporter 3 (ZnT3) gene deleted mice. Zinc transporter 3 knockout (KO) mice had significantly fewer proliferating progenitor cells and immature neurons after hypoglycemia. Our data provide converging evidence in support of the essential role zinc has in modulating hippocampal neurogenesis.
Suh
Sang Won
SW
Department of Neurology, University of California at San Francisco, San Francisco, California, USA. sang.suh@ucsf.edu
Won
Seok Joon
SJ
Hamby
Aaron M
AM
Yoo
Byung Hoon
BH
Fan
Yang
Y
Sheline
Christian T
CT
Tamano
Haruna
H
Takeda
Atsushi
A
Liu
Jialing
J
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins; D049109:Cell Proliferation; D002614:Chelating Agents / Q000008:administration & dosage; D007464:Clioquinol / Q000008:administration & dosage; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007003:Hypoglycemia / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency*
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002614:Chelating Agents; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C491177:Slc30a3 protein, mouse; D007464:Clioquinol; D015032:Zinc