Alzheimer's disease drugs promote neurogenesis.
Alzheimer's disease (AD) is associated with increased production of new neurons (neurogenesis), which may be directed at brain repair. However, the effect of drugs used to treat AD on neurogenesis is unknown. We administered tacrine, galantamine or memantine to mouse cerebral cortical cultures in vitro, and to mice in vivo, and measured neurogenesis by labeling newborn cells with bromodeoxyuridine (BrdU) and confirming their neuronal lineage by cell-type-specific protein expression. All three drugs increased BrdU incorporation into cortical cultures in vitro by up to 40%, and increased BrdU labeling of cells in neuroproliferative regions of the adult mouse brain in vivo by 26-45%. BrdU labeling was associated with neuronal markers, such as Hu and betaIII tubulin. Thus, drugs used to treat AD increase cerebral neurogenesis both in vitro and in vivo, which may contribute to their therapeutic effects.
Jin
Kunlin
K
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Xie
Lin
L
Mao
Xiao Ou
XO
Greenberg
David A
DA
D000818:Animals; D014150:Antipsychotic Agents / Q000145:classification / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*
D014150:Antipsychotic Agents; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine