title: Lithium Restores Age-related Olfactory Impairment in the Ts65Dn Mouse Model of Down Syndrome.
abstract: OBJECTIVE
  Down syndrome, a genetic condition caused by triplication of chromosome 21, is characterized by widespread neurogenesis reduction and cognitive impairment. Unlike other brain functions, smell is not impaired at early life stages and olfactory deterioration begins to appear in adulthood. Similarly to individuals with Down syndrome, in the Ts65Dn mouse model of Down syndrome smell function is normal at early life stages. Smell impairment only appears in adulthood associated with a reduction in the number of new granule neurons migrated to the olfactory bulb from the subventricular zone. Based on evidence that lithium positively impacts neurogenesis, the goal of current study was to establish whether treatment with lithium restores olfactory bulb neurogenesis and olfactory performance in middle-aged Ts65Dn mice.
  
  
  METHODS
  Euploid and Ts65Dn mice aged 13 months were treated with lithium chow or control chow for one month. Before the end of treatment, mice were injected with BrdU, in order to label proliferating cells. Results showed that in Ts65Dn mice lithium treatment restored the number of neural precursor cells in the subventricular zone of the lateral ventricle, rostral migratory stream and olfactory bulb. This effect was accompanied by restoration of olfactory performance. Unlike in olfactory neurogenic regions, treatment had no neurogenesis-enhancing effect on the subgranular zone of the hippocampal dentate gyrus, indicating that lithium has no generalized positive effect on the brain.
  
  
  CONCLUSIONS
  Results suggest that lithium may have a positive impact in brain disorders that, similarly to Down syndrome, are characterized by olfactory decline and neurogenesis impairment in the subventricular zone.
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna. Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Guidi
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna. Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bianchi
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna. Italy.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Stagni
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna. Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacomini
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna. Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Emili
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna. Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Trazzi
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna. Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ciani
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Physiology Building, Piazza di Porta San Donato 2, I-40126 BOLOGNA BO. Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Bartesaghi
mesh_terms: D000367:Age Factors; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D020547:Lateral Ventricles / Q000187:drug effects / Q000502:physiology; D008094:Lithium / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009154:Mutation; D055495:Neurogenesis / Q000187:drug effects*; D000857:Olfaction Disorders / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology; D012903:Smell / Q000187:drug effects* / Q000502:physiology
chemical_list: D008094:Lithium
keywords: Aging; Dentate gyrus; Down syndrome; Lithium; Neurogenesis; Olfactory bulb; Olfactory function; Subventricular
  zone